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RESÚMENES JUNIO 2004 |
Mood - Anxiety Disorders & Antidepressants – Mood Stabilizers
Neuropsychological Dysfunction in Antipsychotic-Naive First-Episode Unipolar Psychotic Depression
S. Kristian Hill, Matcheri S. Keshavan, Michael E. Thase,
and John A. Sweeney
Am J Psychiatry 161:996-1003, June 2004
OBJECTIVE: The
profile of neuropsychological impairment associated with unipolar
psychotic depression remains unclear. The authors used a
neuropsychological test battery to characterize the neuropsychiatric profile
of patients with unipolar psychotic depression, relative to that of
patients with nonpsychotic unipolar depression, patients with
schizophrenia, and healthy comparison subjects. METHOD: Study
subjects included antipsychotic-naive patients with a first episode
of psychotic unipolar depression (N=20), antipsychotic-naive and unmedicated
patients with nonpsychotic unipolar depression (N=14),
antipsychotic-naive patients with first-episode schizophrenia (N=86),
and healthy volunteers (N=81). Groups were matched on age, sex,
race, education, parental socioeconomic status, and estimated
premorbid intelligence. Psychotic patients were followed clinically
for 2 years to confirm diagnosis. All participants completed a
standard neuropsychological battery, including tests of general
intelligence, executive function, attention, verbal memory, motor
skills, and visual-spatial perception. RESULTS: Patients with
psychotic depression had a pattern of neuropsychological dysfunction
that was similar to but less severe than that of patients with
schizophrenia. In contrast, patients with nonpsychotic unipolar
depression had a neuropsychological profile that was similar to that
of healthy individuals but that included mild dysfunction on tests
of attention. Neuropsychological test performance was generally
independent of acute clinical symptoms, but some pairwise group
differences were attenuated by covariation for symptom severity.
CONCLUSIONS: The similar neuropsychological profiles for
schizophrenia and psychotic depression suggest that these psychotic
disorders may have common pathophysiological features. The dramatic
differences in performance between the patients with psychotic
depression and those with nonpsychotic depression point to a marked
distinction in neurocognitive function associated with the
expression of psychosis in depressed patients.
Brain Structural Abnormalities in Psychotropic Drug-Naive Pediatric Patients With Obsessive-Compulsive Disorder
Philip R. Szeszko, Shauna MacMillan, Marjorie McMeniman,
Steven Chen, Keith Baribault, Kelvin O. Lim, Jennifer Ivey, Michelle Rose, S. Preeya
Banerjee, Rashmi Bhandari, Gregory J. Moore, and David R. Rosenberg
Am J Psychiatry 161:1049-1056, June 2004
OBJECTIVE: The
authors investigated structural abnormalities in brain regions
comprising cortical-striatal-thalamic-cortical loops in pediatric
patients with obsessive-compulsive disorder (OCD). METHOD: Volumes
of the caudate nucleus, putamen, and globus pallidus and gray and
white matter volumes of the anterior cingulate gyrus and superior
frontal gyrus were computed from contiguous 1.5-mm magnetic
resonance images from 23 psychotropic drug-naive pediatric patients
with OCD (seven male patients and 16 female patients) and 27 healthy
volunteers (12 male subjects and 15 female subjects). RESULTS:
Patients had smaller globus pallidus volumes than healthy
volunteers, but the two groups did not differ in volumes of the
caudate nucleus, putamen, or frontal white matter regions. Compared
to healthy volunteers, patients had more total gray matter in the
anterior cingulate gyrus but not the superior frontal gyrus. Total
anterior cingulate gyrus volume correlated significantly and
positively with globus pallidus volume in the healthy volunteers but
not in patients. CONCLUSIONS: These findings provide evidence of
smaller globus pallidus volume in patients with OCD without the
potentially confounding effects of prior psychotropic drug exposure.
Volumetric abnormalities in the anterior cingulate gyrus appear
specific to the gray matter in OCD, at least at the gross anatomic
level, and are consistent with findings of functional neuroimaging
studies that have reported anterior cingulate hypermetabolism in
the disorder.
Rapid Antimanic Effect of Risperidone Monotherapy: A 3-Week Multicenter, Double-Blind, Placebo-Controlled Trial
Robert M.A. Hirschfeld, Paul E. Keck, Jr., Michelle Kramer,
Keith Karcher, Carla Canuso, Marielle Eerdekens, and Fred Grossman
Am J Psychiatry 161:1057-1065, June 2004
OBJECTIVE: This
study evaluated the efficacy and safety of risperidone monotherapy
in the treatment of acute bipolar mania. METHOD: Patients with
DSM-IV bipolar I disorder experiencing an acute manic episode
(baseline Young Mania Rating Scale score 
20)
were randomly assigned to 3 weeks of treatment with risperidone (flexible
dose: 1–6 mg/day) or placebo. The primary efficacy measure was the
mean baseline-to-endpoint change in total score on the Young Mania
Rating Scale. Secondary efficacy measures included the Clinical
Global Impression (CGI) severity rating and scores on the
Montgomery-Åsberg Depression Rating Scale, Positive and Negative
Syndrome Scale, and Global Assessment Scale (GAS). Safety
assessments consisted of monitoring adverse events, vital signs,
electrocardiogram and laboratory results, and scores on the
Extrapyramidal Symptom Rating Scale. RESULTS: Subjects (N=259)
received treatment with either risperidone (N=134) or placebo
(N=125). The mean modal dose of risperidone was 4.1 mg/day.
Improvement in mean Young Mania Rating Scale total score (adjusted
for covariates) was significantly greater in the risperidone than in
the placebo group at endpoint (mean change=–10.6 [SD=9.5] versus
–4.8 [SD=9.5], respectively), with significant between-group
differences seen as early as 3 days after start of treatment (change
with risperidone: mean=–6.8 [SD=5.8]; change with placebo: mean=–4.0
[SD=5.8]) and continuing throughout all time points. Improvements in
CGI severity ratings and scores on the Montgomery-Åsberg Depression
Rating Scale, Positive and Negative Syndrome Scale, and GAS were
also significantly greater among patients receiving risperidone than
those given placebo. The most common adverse event reported among
risperidone patients was somnolence. While Extrapyramidal Symptom
Rating Scale scores were significantly greater in patients receiving
risperidone, mean total and subscale scores were low. CONCLUSIONS:
Risperidone monotherapy was significantly more efficacious than
placebo in the treatment of acute mania and demonstrated a rapid
onset of action. Risperidone was well tolerated by patients in this
study.
A Randomized, Placebo-Controlled Trial of Citalopram for the Treatment of Major Depression in Children and Adolescents
Karen Dineen Wagner,
Am J Psychiatry 161:1079-1083, June 2004
OBJECTIVE:
Open-label trials with the selective serotonin reuptake inhibitor
citalopram suggest that this agent is effective and safe for the
treatment of depressive symptoms in children and adolescents. The
current study investigated the efficacy and safety of citalopram
compared with placebo in the treatment of pediatric patients with
major depression. METHOD: An 8-week, randomized, double-blind, placebo-controlled
study compared the safety and efficacy of citalopram with placebo in
the treatment of children (ages 7–11) and adolescents (ages 12–17)
with major depressive disorder. Diagnosis was established with the
Schedule for Affective Disorders and Schizophrenia for School-Age Children—Present
and Lifetime Version. Patients (N=174) were treated initially with
placebo or 20 mg/day of citalopram, with an option to increase the
dose to 40 mg/day at week 4 if clinically indicated. The primary
outcome measure was score on the Children’s Depression Rating
Scale—Revised; the response criterion was defined as a score of 
28.
RESULTS: The overall mean citalopram dose was approximately 24
mg/day. Mean Children’s Depression Rating Scale—Revised scores
decreased significantly more from baseline in the citalopram treatment
group than in the placebo treatment group, beginning at week 1 and
continuing at every observation point to the end of the study
(effect size=2.9). The difference in response rate at week 8 between
placebo (24%) and citalopram (36%) also was statistically
significant. Citalopram treatment was well tolerated. Rates of
discontinuation due to adverse events were comparable in the placebo
and citalopram groups (5.9% versus 5.6%, respectively). Rhinitis,
nausea, and abdominal pain were the only adverse events to occur
with a frequency exceeding 10% in either treatment group.
CONCLUSIONS: In this population of children and adolescents, treatment
with citalopram reduced depressive symptoms to a significantly greater
extent than placebo treatment and was well tolerated.
Lithium facilitates apoptotic signaling induced by
activation of the Fas death domain-containing receptor
Ling
Song, Tong Zhou and Richard S Jope
BMC
Neuroscience 2004, 5:20
Background
Lithium,
a mood stabilizer widely used to treat bipolar disorder, also is a
neuroprotectant, providing neurons protection from apoptosis induced by a broad
spectrum of toxic conditions. A portion of this neuroprotection is due to
lithium's inhibition of glycogen synthase kinase-3. The present investigation
examined if the neuroprotection provided by lithium included apoptosis induced
by stimulation of the death domain-containing receptor Fas.
Results
Instead
of providing protection, treatment with 20 mM lithium significantly increased
apoptotic signaling induced by activation of Fas, and this occurred in both
Jurkat cells and differentiated immortalized hippocampal neurons. Other
inhibitors of glycogen synthase kinase-3, including 20 microM
indirubin-3'-monoxime, 5 microM kenpaullone, and 5 microM rottlerin, also
facilitated Fas-induced apoptotic signaling, indicating that the facilitation
of apoptosis by lithium was due to inhibition of glycogen synthase kinase-3.
Conclusions
These
results demonstrate that lithium is not always a neuroprotectant, and it has
the opposite effect of facilitating apoptosis mediated by stimulation of death
domain-containing receptors.
Adrian J. Lloyd,
The British Journal of Psychiatry (2004)
184: 488-495
Background
Evidence for structural hippocampal change in depression is limited
despite reports of neuronal damage due to hypercortisolaemia and
vascular pathology.
Aims To
compare hippocampal and white matter structural change in
demographically matched controls and participants with early-onset and
late-onset depression.
Method
High-resolution volumetric magnetic resonance imaging (MRI) and
rating of MRI hyperintensities.
Results
Atotal of 51 people with depression and 39 control participants were
included. Participants with late-onset depression had bilateral hippocampal
atrophy compared with those with early-onset depression and
controls. Hippocampal volumes did not differ between control participants
and those with early-onset depression. Age of depression onset
correlated (negatively) with hippocampal volume but lifetime
duration of depression did not. Hyperintensity ratings did not
differ between groups.
Conclusions
Results suggest that acquired biological factors are of greater
importance in late-than in early-onset illness and that pathological
processes other than exposure to hypercortisolaemia of depression
underlie hippocampal atrophy in depression of late life.
Hypothalamic-pituitary-adrenal axis function in patients with bipolar
disorder
Stuart Watson, James C. Ritchie,
The British Journal of Psychiatry (2004)
184: 496-502
Background
Hypothalamic-pituitary-adrenal (HPA) axis function, as variously
measured by the responses to the combined
dexamethasone/corticotrophin-releasing hormone (dex/CRH) test, the
dexamethasone suppression test (DST) and basal cortisol levels, has
been reported to be abnormal in bipolar disorder.
Aims To
test the hypothesis that HPA axis dysfunction persists in patients
in remission from bipolar disorder.
Method
Salivary cortisol levels and the plasma cortisol response to the DST
and dex/CRH test were examined in 53 patients with bipolar disorder,
27 of whom fulfilled stringent criteria for remission, and in 28
healthy controls. Serum dexamethasone levels were measured.
Results
Patients with bipolar disorder demonstrated an enhanced cortisol
response to the dex/CRH test compared with controls (P=0.001). This
response did not differ significantly between remitted and
non-remitted patients. These findings were present after the
potentially confounding effects of dexamethasone levels were
accounted for.
Conclusions
The dex/CRH test is abnormal in both remitted and non-remitted
patients with bipolar disorder. This measure of HPA axis dysfunction
is a potential trait marker in bipolar disorder and thus possibly
indicative of the core pathophysiological process in this illness.
The effect of duloxetine on painful physical symptoms in depressed patients:
do improvements in these symptoms result in higher remission rates?
Fava M,
Mallinckrodt CH, Detke MJ, Watkin JG, Wohlreich MM.
Journal
of clinical psychiatry 2004;65(4):521-530.
BACKGROUND:
Depression is a chronic disease consisting of emotional/psychological and
physical symptoms. Emotional symptoms have been shown to respond to currently
available antidepressants; however, physical symptoms may not be as responsive.
It was hypothesized that resolution of both psychological and physical symptoms
of depression would predict a higher percentage of patients achieving remission.
METHOD: Efficacy data were pooled from 2 identical, but independent, 9-week
randomized, double-blind clinical trials of duloxetine 60 mg q.d. (N = 251) and
placebo (N = 261). All patients met diagnostic criteria for DSM-IV major
depressive disorder, which was confirmed by the Mini-International
Neuropsychiatric Interview. Efficacy measures included the 17-item Hamilton
Rating Scale for Depression (HAM-D-17) total score, the HAM-D-17 Maier
subscale, the Clinical Global Impressions-Severity of Illness (CGI-S) scale,
the Patient Global Impression of Improvement (PGI-I) scale, the Somatic Symptom
Inventory, the Quality of Life in Depression Scale, and Visual Analog Scales
(VAS) for pain (overall pain, headaches, back pain, shoulder pain, interference
with daily activities, and time in pain while awake). RESULTS:
Duloxetine-treated patients demonstrated significantly greater improvement in
overall pain (p =.016), back pain (p =.002), and shoulder pain (p =.021) at
week 9 compared with patients receiving placebo. When treatment effects were
pooled over all visits, patients receiving duloxetine, 60 mg q.d., exhibited
significantly greater improvement than placebo-treated patients in 5 of the 6
assessed VAS pain measures. Approximately 50% of the improvement in overall
pain was independent of improvement in HAM-D-17 total score. Assuming the same
level of improvement in core emotional symptoms of depression (Maier subscale),
improvement in overall pain severity was associated with higher estimated
probabilities of remission (p <.001). The week 9 means for VAS overall pain
severity were 13.0 for remitters (last observed value for HAM-D-17 was < or
= 7) compared with 22.7 for nonremitters (p <.001), respectively,
representing a greater than 3-fold improvement from baseline in remitters. The
remission rate for pain responders (improvement in VAS overall pain from
baseline to last observation > or = 50%) was twice that observed for pain
nonresponders (36.2% vs. 17.8%, p <.001). Greater improvements in pain outcomes
were associated with more favorable endpoint outcomes on the CGI-S and PGI-I
scales. In addition, early favorable responses in VAS overall pain severity
were associated with favorable endpoint outcomes. CONCLUSIONS: Treatment with
duloxetine, 60 mg q.d., significantly reduced pain compared with placebo.
Improvements in pain severity were attributable equally to the direct effect of
duloxetine and to associated changes in depression severity. Improvement in
painful physical symptoms was associated with higher remission rates even after
accounting for improvement in core emotional symptoms.
Single photon emission computed tomography in
posttraumatic stress disorder before and after treatment with a selective
serotonin reuptake inhibitor.
Seedat S,
Warwick J, van Heerden B, Hugo C, Zungu-Dirwayi N, Van Kradenburg J, Stein DJ.
J Affect Disord. 2004 May;80(1):45-53.
BACKGROUND: Posttraumatic stress disorder (PTSD) is recognized as a disorder
mediated by specific neurobiological circuits. Functional imaging studies using
script-driven trauma imagery and pharmacological challenges have documented
altered cerebral function (activation and deactivation) in several brain
regions, including the amygdala, hippocampus, prefrontal cortex and anterior
cingulate. However, the neural substrates of PTSD remain poorly understood and
the effect of selective serotonin reuptake inhibition on regional cerebral
activity is deserving of further investigation. METHODS: Eleven adult patients
(seven men, four women) (mean age+S.D.=33.6+/-9.2 years) with a DSM-IV
diagnosis of PTSD, as determined by the Structured Clinical Interview for
DSM-IV (SCID-I) and the Clinician-Administered PTSD Scale (CAPS), underwent
single photon emission computed tomography (SPECT) with Tc-99m HMPAO pre- and
post-8 weeks of treatment with the selective serotonin reuptake inhibitor,
citalopram. Symptoms were assessed at baseline and at 2-week intervals with the
Clinician-Administered PTSD Scale (CAPS), Montgomery-Asberg Depression Rating
Scale (MADRS), and the Clinical Global Impression Scale (CGI). Image analysis
of baseline and post-treatment scans was performed using Statistical Parametric
Mapping (SPM). RESULTS: Treatment with citalopram resulted in significant
deactivation in the left medial temporal cortex irrespective of clinical
response. On covariate analysis, a significant correlation between CAPS score
reduction and activation in the left paracingulate region (medial prefrontal
cortex) was observed post-treatment. No significant pre-treatment differences were
observed between responders and non-responders in anterior cingulate perfusion.
CONCLUSIONS: These preliminary findings are consistent with clinical data
indicating temporal and prefrontal cortical dysfunction in PTSD and preclinical
data demonstrating serotonergic innervation of these regions. However, further
studies, in particular in vivo receptor imaging studies, are needed to confirm
whether these regional abnormalities correlate with clinical features and
treatment response.
Treatment
and response in refractory depression: results from a specialist affective
disorders service
N.
Kennedy and E. S. Paykel
Journal of Affective Disorders .Volume 81, Issue 1 , July 2004, Pages 49-53
Background:
The best treatment approaches for chronic severe refractory depression remain
uncertain. This study aimed to identify short-term outcome and most successful
somatic treatments of severe refractory depressives referred to an affective
disorders service. Methods: Patients with chronic refractory depression
referred to a specialist affective disorders service over a 10-year period were
studied. Using detailed case records of the index episode, courses of treatment
and outcome were examined. Results: Patients were predominantly middle-aged
females with few prior episodes but long index episodes. Patients received
higher antidepressant doses and more combinations on the specialist service.
Very-high-dose antidepressants (tricyclics, velafaxine or tricyclic–MAOI
combinations), usually augmented with lithium and often combined with ECT, were
the most effective somatic treatments. Most subjects improved substantially,
but few reached premorbid levels. Limitations: The study was retrospective.
Treatment courses were sequential rather than random. Conclusions: Refractory
depression is responsive to vigorous somatic therapy, although most patients
continue with some symptoms.
Gabriel
Rubio, Luis San, Francisco López-Muñoz and Cecilio Alamo
Journal of Affective Disorders .Volume 81, Issue 1 , July 2004, Pages 67-72
Background:
To investigate the usefulness of the combination therapy with two
antidepressants from different pharmacological families in treatment-resistant
depressive patients. Methods: In this prospective 6 weeks open-label study, we
assessed the effectiveness of the addition of reboxetine to 61 depressive
patients that had previously not responded, or had done so only in a partial
way, to conventional treatment, in monotherapy, with selective serotonin
reuptake inhibitors (SSRIs), venlafaxine or mirtazapine. Data were analyzed on
an intent-to-treat basis, using the last-observation-carried-forward (LOCF)
method. Results: Mean decrease on the 21-item Hamilton Depression Rating Scale
(HDRS) score was 48.9% and on the Clinical Global Impressions Scale (CGI),
38.9%. At the end of the treatment, 62.3% of the patients were evaluated as
improvement (CGI<4), 54.1% as responders (HDRS≤50%) and 45.9% in
remission (HDRS≤10). No serious side effects were observed during
combination therapy, being more frequent increased sweating (8.2%) and dry
mouth (6.6%). Conclusions: These findings suggest that the strategy of
combination with reboxetine may be an effective and well-tolerated tool in
treatment-resistant patients who have failed to adequately respond to
monotherapy with SSRIs, venlafaxine or mirtazapine.
The
selective serotonin reuptake inhibitor citalopram increases fear after acute
treatment but reduces fear with chronic treatment: a comparison with tianeptine
Nesha S.
Burghardt, Gregory M. Sullivan, Bruce S. McEwen, Jack M. Gorman and Joseph E.
LeDoux
Biological Psychiatry .Volume 55, Issue 12 , 15 June 2004, Pages
1171-1178
Background
Selective
serotonin reuptake inhibitors (SSRIs) are efficacious in the treatment of a
variety of fear or anxiety disorders. Although they inhibit the reuptake of
serotonin within hours of administration, therapeutic improvement only occurs
after several weeks. In this study, we used fear conditioning to begin to
understand how acute and chronic SSRI treatment might differentially affect
well-characterized fear circuits.
Methods
We
evaluated the effects of acute and chronic treatment with the SSRI citalopram
on the acquisition of auditory fear conditioning. To further understand the
role of serotonin in modulating fear circuits, we compared these effects with
those of acute and chronic administration of the antidepressant tianeptine, a
purported serotonin reuptake enhancer.
Results
We found
that acute administration of the SSRI citalopram enhanced acquisition, whereas
chronic treatment reduced the acquisition of auditory fear conditioning. In
comparison, treatment with tianeptine had no effect acutely but also reduced
the acquisition of tone conditioning when administered chronically.
Conclusions
Our
findings with citalopram are consistent with the clinical effects of SSRI
treatment seen in patients with anxiety disorders, in which anxiety is often
increased during early stages of treatment and decreased after several weeks of
treatment. The findings also indicate that auditory fear conditioning can be a
useful tool in understanding differences in the effects of short-term and
long-term antidepressant treatment with serotonergic medications.
One
year cumulative incidence of depression following myocardial infarction and
impact on cardiac outcome
Jacqueline
J. M. H. Strik, Richel Lousberg, Emile C. Cheriex and Adriaan Honig
Journal of Psychosomatic Research .Volume 56, Issue 1 , January 2004, Pages
59-66
Background
Major
depression has been identified as an independent risk factor for increased
morbidity and mortality in mixed patients populations with first and recurrent
myocardial infarction (MI). The aim of this study was to evaluate whether
incidence of major and minor depression is as high in a population with merely
first-MI patients as in recurrent MI populations. Furthermore, it was evaluated
whether in first-MI patients major and minor depression, and depressive
symptoms, had an impact on cardiac mortality and morbidity up to 3 years post
MI.
Methods
A
consecutive cohort of 206 patients with a first MI were included in this study.
One month following MI, all patients were interviewed using the Structured
Clinical Interview for DSM-IV (SCID-I-R). Three, six, nine and twelve months
following MI, patients filled out three psychiatric self-rating scales for
depression, the Beck Depression Inventory (BDI), the Hospital Anxiety and
Depression Scale (HADS), and the 90-item Symptom Checklist (SCL-90). Patients,
exceeding a previously defined cut-off value on at least one of these scales,
were reinterviewed using the SCID. The BDI was applied to assess depressive
symptoms in relation to cardiac outcome as the SCL-90 and HADS showed similar
results. Cardiac outcome was defined as major cardiac event, i.e., death or
recurrent MI, and health care consumption, i.e., cardiac rehospitalisation
and/or frequent visits at the cardiac outpatient clinic. Depression outcome was
assessed from 1 month post MI up to 1 year post MI whereas cardiac outcome was
assessed between 1 month and 3 years post MI.
Results
A 1-year
incidence of 31% of major and minor depression was found in first-MI patients.
The highest incidence rate for both major and minor depression was found in the
first month after MI. Compared with nondepressed patients, depressed patients
were younger (P=.001), female (P=.04) and were known with a previous depressive
episode (P=.002). Neither major/minor depression nor depressive symptoms
significantly predicted major cardiac events, but did predict health care
consumption (P=.04 and P<.001, respectively).
Conclusions
Incidence
of major and minor depression is similar in this first-MI patients population
as in recurrent MI populations. Major/minor depressive disorder nor depressive
symptoms predicted neither mortality nor reinfarction.
Mani N.
Pavuluri, Ellen S. Herbener and John A. Sweeney
Journal of Affective Disorders .Volume 80, Issue 1 , May 2004, Pages 19-28
Background:
There is under-recognition or misdiagnosis of pediatric bipolar disorder with
psychotic features. It is of major public health importance to recognize
psychosis in bipolar disorder. Method: Original research on phenomenological
description of psychosis and external validators including family history,
longitudinal course and treatment effects are systematically reviewed. Age
differences, sampling, and interview methods of the studies on pediatric
bipolar disorder that reported psychotic features are compared. Critical
differentiating features between pediatric bipolar disorder and pediatric
schizophrenia are summarized given the presence of overlapping psychotic
features. Results: Prevalence of psychotic features in pediatric bipolar
disorder ranged from 16 to 87.5% based on age and methodological differences.
The most common psychotic features are mood congruent delusions, mainly
grandiose delusions. Psychotic features appear in the context of affective
symptoms in pediatric bipolar disorder as opposed to schizophrenia where
psychotic symptoms are independent of them. Family history of affective psychosis
aggregated in probands with bipolar disorder. Limitations: There is discrepancy
in clinical appraisal of what constitutes psychosis and pediatric bipolar
disorder, apart from the differences in methodology and nature of the samples.
Conclusion: Clinicians must be vigilant in identifying psychosis in pediatric
bipolar disorder, especially when there is a positive family history of
psychosis.
Differential
response of bipolar and normal control lymphoblastoid cell sodium pump to
ethacrynic acid
Rena Li
and Rif S. El-Mallakh
Journal of Affective Disorders .Volume 80, Issue 1 , May 2004, Pages 11-17
Background:
While the pathogenesis of manic-depressive, or bipolar, illness is unknown, an
excess of intracellular sodium and calcium concentrations is thought to
contribute to the development of the illness. Previous work has demonstrated a
reduced adaptive response of the sodium pump to ethacrynic acid in lymphocytes
obtained from bipolar subjects compared to psychiatrically normal controls.
Methods: To further examine this phenomenon, we investigated several aspects of
sodium pump response (transcription, translation, activity, and intracellular
ion concentration) in lymphoblastoid cell lines derived from bipolar subjects
and matched normal controls. Cells were treated with ethacrynic acid 100 
M
for 3 days. Results:
Single
photon emission computed tomography in posttraumatic stress disorder before and
after treatment with a selective serotonin reuptake inhibitor
Soraya
Seedat, James Warwick, Barend van Heerden, Charmaine Hugo, Nompumelelo
Zungu-Dirwayi, Jeanine Van Kradenburg, and Dan J. Stein
Journal of Affective Disorders .Volume 80, Issue 1 , May 2004, Pages 45-53
Background:
Posttraumatic stress disorder (PTSD) is recognized as a disorder mediated by
specific neurobiological circuits. Functional imaging studies using
script-driven trauma imagery and pharmacological challenges have documented
altered cerebral function (activation and deactivation) in several brain
regions, including the amygdala, hippocampus, prefrontal cortex and anterior
cingulate. However, the neural substrates of PTSD remain poorly understood and
the effect of selective serotonin reuptake inhibition on regional cerebral
activity is deserving of further investigation. Methods: Eleven adult patients
(seven men, four women) (mean age+S.D.=33.6±9.2 years) with a DSM-IV diagnosis
of PTSD, as determined by the Structured Clinical Interview for DSM-IV (SCID-I)
and the Clinician-Administered PTSD Scale (CAPS), underwent single photon
emission computed tomography (SPECT) with Tc-99m HMPAO pre- and post-8 weeks of
treatment with the selective serotonin reuptake inhibitor, citalopram. Symptoms
were assessed at baseline and at 2-week intervals with the
Clinician-Administered PTSD Scale (CAPS), Montgomery–Asberg Depression Rating
Scale (MADRS), and the Clinical Global Impression Scale (CGI). Image analysis
of baseline and post-treatment scans was performed using Statistical Parametric
Mapping (SPM). Results: Treatment with citalopram resulted in significant
deactivation in the left medial temporal cortex irrespective of clinical
response. On covariate analysis, a significant correlation between CAPS score
reduction and activation in the left paracingulate region (medial prefrontal
cortex) was observed post-treatment. No significant pre-treatment differences
were observed between responders and non-responders in anterior cingulate
perfusion. Conclusions: These preliminary findings are consistent with clinical
data indicating temporal and prefrontal cortical dysfunction in PTSD and
preclinical data demonstrating serotonergic innervation of these regions.
However, further studies, in particular in vivo receptor imaging studies, are
needed to confirm whether these regional abnormalities correlate with clinical
features and treatment response.
Correlation
between cerebral blood flow and items of the
Ariel Graff-Guerrero,
Jorge González-Olvera, Yazmín Mendoza-Espinosa, Víctor Vaugier and Juan Carlos
García-Reyna
Journal of Affective Disorders .Volume 80, Issue 1 , May 2004, Pages 55-63
Background:
The purpose of this study was to correlate the basal cerebral blood flow (CBF)
in patients with major depressive disorder (MDD) with the score for each of the
21 questions in the Hamilton Rating Scale for Depression (HRSD), in order to
determine the cerebral regions associated with each item. Methods: Fourteen
antidepressant-naive patients with unipolar depression (DSM-IV criteria for MDD)
participated in this study with a HRSD score of ≥20 points. CBF images
obtained by SPECT were analyzed by SPM99 software. The significant correlation
threshold for a priori regions (frontocortical and limbic regions) was a Z
value of at least 2.25 and clusters formed by more than 10 voxels. Results:
Items 1, 6, 11 and 20 were positively correlated with right medial frontal
gyrus; item 7 was negatively correlated with bilateral medial frontal gyrus.
Items 2 and 10 were positively correlated with right anterior and medial
cingulate, respectively. Item 5 was negatively correlated with the left
amygdala. Item 9 was negatively correlated with bilateral insula, and item 16
with right insula. Items 12 and 14 were positively correlated with right and
left precentral frontal gyrus, respectively. Limitations: The small sample size
and only out-patients included in the study. Conclusions: The frontal cortex
plays an important role in the expression of MDD symptoms. Not all the symptoms
evaluated correlated with one single structure, which may explain the diverse
results reported in the literature. These preliminary results support the
necessity of further analyses by symptoms that could provide more specific
information on the pathophysiology of MDD.
Measurement of Brain Regional 
-[11C]Methyl-L-Tryptophan
Trapping as a Measure of Serotonin Synthesis in Medication-Free Patients With
Major Depression
Pedro Rosa-Neto, Mirko Diksic, Hidehiko Okazawa,
Marco Leyton, Nayyer Ghadirian, Shadreck Mzengeza, Akio Nakai, Guy Debonnel,
Pierre Blier, Chawki Benkelfat
Arch Gen Psychiatry. 2004;61:556-563.
Context The serotonin hypothesis of
depression invokes a relative or absolute deficit of serotonin
neurotransmission. Reduced synthesis of serotonin in the brain
pathways mediating the expression of mood (ie, the limbic cortex) is
a plausible candidate mechanism.
Objectives To measure and compare, using the 
-[11C]methyl-L-tryptophan/positron
emission tomography method, the brain trapping constant of -[11C]methyl-L-tryptophan
(K*, milliliters per gram per minute), an index of serotonin synthesis,
in brain areas involved in the regulation of mood in patients with
major depression (MD) and age- and sex-matched controls.
Design Between-group comparison.
Setting Department of Psychiatry and
Participants Seventeen medication-free
outpatients with a current episode of MD (9 women: mean ± SD age, 41
± 11 years; 8 men: mean ± SD age, 41 ± 11 years) and 17
controls (9 women: mean ± SD age, 37 ± 15 years; 8 men: mean ± SD
age, 32.5 ± 9.9 years).
Main Outcome Measure Normalized K*,
normalized to the global mean, was measured in the dorsolateral
prefrontal, anterior cingulate, and mesial temporal cortices; the
thalamus; and the caudate nucleus.
Results Compared with age- and sex-matched
controls, normalized K* was significantly decreased bilaterally in
female patients with MD in the anterior cingulate cortex, in the
left anterior cingulate cortex in male patients with MD, and in the
left mesial temporal cortex in male and female patients with MD
(P<.001 for all). Exploratory analyses identified additional
patient-control differences for normalized K* (eg, inferior frontal
gyrus and superior parietal lobule), most of which, once corrected
for 38 multiple comparisons, lost their significance. Morphometric
measurements of the cingulate cortex divisions confirmed that the
reduction of normalized K* in depressed patients was not attributable
to a reduction in gray matter volume. Normalized K* in the anterior
cingulate cortex did not correlate with ratings of depression
severity collected at the time of scan.
Conclusions Reduction of normalized K*, an
index of serotonin synthesis, in parts of the limbic and paralimbic
cortices may contribute to the biochemical alterations associated
with MD.
Distinct Neural Correlates of
Washing, Checking, and Hoarding Symptom Dimensions in Obsessive-compulsive
Disorder
David Mataix-Cols, Sarah Wooderson, Natalia
Lawrence, Michael J. Brammer, Anne Speckens, Mary L. Phillips
Arch Gen Psychiatry. 2004;61:564-576.
Context Obsessive-compulsive disorder (OCD)
is clinically heterogeneous, yet most previous functional
neuroimaging studies grouped together patients with mixed symptoms,
thus potentially reducing the power and obscuring the findings of
such studies.
Objective To investigate the neural
correlates of washing, checking, and hoarding symptom dimensions in
OCD.
Design Symptom provocation paradigm,
functional magnetic resonance imaging, block design, and
nonparametric brain mapping analyses.
Setting University hospital.
Participants Sixteen patients with OCD (11
inpatients, 5 outpatients) with mixed symptoms and 17 healthy
volunteers of both sexes.
Intervention All subjects participated in 4
functional magnetic resonance imaging experiments. They were scanned
while viewing alternating blocks of emotional (washing-related,
checking-related, hoarding-related, or aversive, symptom-unrelated)
and neutral pictures, and imagining scenarios related to the content
of each picture type.
Main Outcome Measure Blood oxygenation
level–dependent response.
Results Both patients and control subjects
experienced increased subjective anxiety during symptom provocation
(patients significantly more so) and activated neural regions
previously linked to OCD. Analyses of covariance, controlling for
depression, showed a distinct pattern of activation associated with
each symptom dimension. Patients demonstrated significantly greater
activation than controls in bilateral ventromedial prefrontal regions
and right caudate nucleus (washing); putamen/globus pallidus,
thalamus, and dorsal cortical areas (checking); left precentral
gyrus and right orbitofrontal cortex (hoarding); and left
occipitotemporal regions (aversive, symptom-unrelated). These
results were further supported by correlation analyses within
patients, which showed highly specific positive associations between
subjective anxiety, questionnaire scores, and neural response in
each experiment. There were no consistently significant differences
between patients with (n = 9) and without (n = 7) comorbid
diagnoses.
Conclusions The findings suggest that
different obsessive-compulsive symptom dimensions are mediated by
relatively distinct components of frontostriatothalamic circuits
implicated in cognitive and emotion processing. Obsessive-compulsive
disorder may be best conceptualized as a spectrum of multiple,
potentially overlapping syndromes rather than a unitary nosologic
entity.
Update on neurosurgical treatment for obsessive compulsive disorder.
LOPES, Antonio Carlos, MATHIS, Maria Eugênia de, CANTERAS, Miguel Montes et al.
Rev. Bras. Psiquiatr., Mar. 2004, vol.26, no.1,
p.62-66.
Responses
to pharmacotherapy and psychotherapy in obsessive-compulsive disorder (OCD)
range from 60 to 80% of cases. However, a subset of OCD patients do not respond
to adequately conducted treatment trials, leading to severe psychosocial
impairment. Stereotactic surgery can be indicated then as the last resource.
Five surgical techniques are available, with the following rates of global
post-operative improvement: anterior capsulotomy (38-100%); anterior
cingulotomy (27-57%); subcaudate tractotomy (33-67%); limbic leucotomy
(61-69%), and central lateral thalamotomy/anterior medial pallidotomy (62.5%).
The first technique can be conducted as a standard neurosurgery, as
radiosurgery or as deep brain stimulation. In the standard neurosurgery neural
circuits are interrupted by radiofrequency. In radiosurgery, an actinic lesion
is provoked without opening the brain. Deep brain stimulation consists on
implanting electrodes which are activated by stimulators. Literature reports a
relatively low prevalence of adverse events and complications.
Neuropsychological and personality changes are rarely reported. However, there
is a lack of randomized controlled trials to prove efficacy and adverse
events/complication issues among these surgical procedures. Concluding, there is
a recent development in the neurosurgeries for severe psychiatric disorders in
the direction of making them more efficacious and safer. These surgeries, when
correctly indicated, can profoundly alleviate the suffering of severe OCD
patients.
Implication of the hypothalamic–pituitary–adrenal
axis in the physiopathology of depression
Nicholas Barden
J Psychiatry
Neurosci. 2004 May; 29 (3): 185–193
Major alterations of the
hypothalamic–pituitary–adrenocortical (HPA) system that can be reversed by
successful antidepressant therapy are often seen in depressed patients.
Persuasive evidence points to the involvement of a dysfunctional glucocorticoid
receptor (GR) system in these changes. Support for this also comes from studies
of transgenic mice that express an antisense RNA, complementary to the GR mRNA,
and have numerous neuroendocrine characteristics of human depression as well as
altered behaviour. Many of these neuroendocrine and behavioural characteristics
of the transgenic mice can be reversed by antidepressants. A possible
explanation for this is that the antidepressant-induced increase in GRs renders
the HPA axis more sensitive to glucocorticoid feedback. This new insight into
antidepressant drug action suggests a novel approach to the development of antidepressant
drugs.
Implications of adult hippocampal
neurogenesis in antidepressant action
Jessica E. Malberg
J Psychiatry
Neurosci. 2004 May; 29 (3): 196–205
In the dentate gyrus of the
hippocampus, cell birth and maturation into neurons, or neurogenesis, occur
throughout the lifetime of animals and humans. Multiple factors have been shown
to regulate adult neurogenesis, and a number of findings in this field have had
a large impact on basic and clinical research in depression. It has been
reported that both physical and psychosocial stress paradigms, as well as some
animal models of depression, produce a decrease in hippocampal cell
proliferation and neurogenesis. Conversely, long-term, but not short-term,
treatment with different classes of antidepressant drug increases cell
proliferation and neurogenesis. Patients with depressive disorders or
post-traumatic stress disorder have reduced hippocampal volume. Given this
interaction of stress, depression and neurogenesis, a current hypothesis is
that reduced adult hippocampal cell proliferation or neurogenesis may be
involved in the pathophysiology of depression and that reversal or prevention
of the decrease in neurogenesis may be one way in which the antidepressant
drugs exert their effects. Research from this emerging field will further our
understanding of the effects of stress and depression on the brain and the
mechanism of action of antidepressant drugs.
Impact of substance P receptor antagonism on the
serotonin and norepinephrine systems: relevance to the
antidepressant/anxiolytic response
Pierre Blier,
Gabriella Gobbi, Nasser Haddjeri, Luca Santarelli,
Gina Mathew, and René Hen
J Psychiatry
Neurosci. 2004 May; 29 (3): 208–218
Substance P (neurokinin-1 [NK1])
receptor antagonists appear to be effective antidepressant and anxiolytic
agents, as indicated in 3 double-blind clinical trials. In laboratory animals,
they promptly attenuate the responsiveness of serotonin (5-hydroxytryptamine
[5-HT]) and norepinephrine (NE) neurons to agonists of their cell-body
autoreceptors, as is the case for some antidepressant drugs that are currently
in clinical use. Long-term, but not subacute, antagonism of NK1 receptors in
rats increases 5-HT transmission in the hippocampus, a property common to all
antidepressant treatments tested thus far. This enhancement seems to be
mediated by a time-dependent increase in the firing rate of 5-HT neurons. Mice
with the NK1 receptor deleted from their genetic code also have an increased
firing rate of 5-HT neurons. Taken together, these observations strongly
suggest that NK1 antagonists could become a new class of antidepressant and
anxiolytic agents.
Three year naturalistic outcome study of panic
disorder patients treated with paroxetine
Pinhas
N Dannon, Iulian Iancu, Katherine Lowengrub, Ami Cohen, Leon J Grunhaus and
Moshe Kotler
BMC
Psychiatry 2004, 4:16
Background
This
naturalistic open label follow up study had three objectives:1. To observe the
couse of ilness in panic disorder (PD) patients receiving long term and
intermediate term paroxetine treatment 2. to compare relapse rates and side
effect profile between these two groups 3. to obseve paroxetine's tolerability
over 24 month period.
Methods
143
patients with PD with or w/o agoraphobia completed 12 moth paroxetine
treatment. At the end of this period 71 of the patients received vanother
twelve months of treatment with paroxetine while 72 of them discontinued. All
these two groups monitored another twelve months while med-free.
Results
Only 21
of 143 relapsed. No significant differences noticed between 12 moths and 24
months of paroxetine treatment. 43 patients reported sexual side effects and
the average weight gain was 5.06 kg during the treatment. All the patients who
eventually relapsed demonstrated significantly greater weight increase during
the treatment phase.
Conclusions
the
extension of paroxetine treatment more than a year did not seem further
decrease the risk of relaps
Pathophysiology
of obsessive-compulsive disorder: A necessary link between phenomenology,
neuropsychology, imagery and physiology.
Aouizerate B, Guehl D, Cuny E, et al.
Prog Neurobiol 2004;72(3):195-221.
Obsessive-compulsive disorder (OCD) is characterized by repetitive
intrusive thoughts and compulsive time-consuming behaviors classified into three
to five distinct symptom dimensions including: (1) aggressive/somatic
obsessions with checking compulsions; (2) contamination concerns with washing
compulsions; (3) symmetry obsessions with counting/ordering compulsions; (4)
hoarding obsessions with collecting compulsions; and (5) sexual/religious
concerns. Phenomenologically, OCD could be thought of as the irruption of
internal signals centered on the erroneous perception that "something is
wrong" in a specific situation. This generates severe anxiety, leading to
recurrent behaviors aimed at reducing the emotional tension. In this paper, we
examine how the abnormalities in brain activity reported in OCD can be
interpreted in the light of physiology after consideration of various
approaches (phenomenology, neuropsychology, neuroimmunology and neuroimagery)
that contribute to proposing the central role of several cortical and
subcortical regions, especially the orbitofrontal cortex (OFC), the anterior
cingulate cortex (ACC), the dorsolateral prefrontal cortex (DLPC), the head of
the caudate nucleus and the thalamus. The OFC is involved in the significance
attributed to the consequences of action, thereby subserving decision-making,
whereas the ACC is particularly activated in situations in which there are conflicting
options and a high likelihood of making an error. The DLPC plays a critical
part in the cognitive processing of relevant information. This cortical
information is then integrated by the caudate nucleus, which controls
behavioral programs. A dysfunction of these networks at one or several stages
will result in the emergence and maintenance of repetitive thoughts and
characteristic OCD behavior.
Metabolism
of the newest antidepressants: comparisons with related predecessors.
Caccia S.
IDrugs : the investigational drugs journal
2004;7(2):143-150.
The need for better acute and long-term treatment for depressive
disorders has led to the development of new agents, including escitalopram,
duloxetine, and gepirone. These drugs undergo extensive biotransformation, with
cytochrome P450 (CYP) isoforms playing a major role. Escitalopram is
biotransformed by CYP2C19, CYP3A4 and CYP2D6; partly extrapolating from studies
of citalopram, polymorphism at CYP2C19 and drug interactions at CYP2D6 may be
clinically significant. Duloxetine is metabolized by CYP2D6 and CYP1A2, with
moderate potential for interactions at CYP2D6. The metabolism of gepirone
involves CYP3A4 and to a lesser extent CYP2D6.
Increased risk of developing diabetes in depressive and bipolar
disorders?
Lars
Vedel Kessing, Flemming Mørkeberg Nilsson, Volkert Siersma and Per Kragh
Andersen
Journal of Psychiatric Research .Volume 38, Issue 4 , July-August 2004,
Pages 395-402
A few
studies have suggested that the prevalence of diabetes is increased for
patients with depression and for patients with bipolar disorder compared with
the general population. However, no study has been published comparing the risk
of getting a diagnosis of diabetes
for patients with affective disorders with the risk for patients with other
medical illnesses. It was the aim of the present study to investigate whether
patients hospitalised for depressive or bipolar disorders are at increased risk
of getting a diagnosis of diabetes
at readmission compared to patients previously admitted for osteoarthritis. In
a nationwide case register study, all patients who got a discharge diagnosis of
depression, mania/bipolar disorder or osteoarthritis at first admission in a
period from 1977 to 1997 were identified. The probability of getting readmitted
and discharged with a diagnosis of diabetes
was estimated with competing risks models in survival analysis. In total,
29,035 patients with a diagnosis of depression at first discharge, 6683
patients with mania/mixed episode and 108,525 patients with a diagnosis of
osteoarthritis were identified. The risk of getting readmitted with diabetes was not increased for patients
who had previously been admitted with depression or mania/bipolar disorder
compared to patients with osteoarthritis. There was no difference in the risks
of developing Type 1 and Type 2 diabetes.
Trans-cultural
aspects of obsessive–compulsive disorder: a description of a Brazilian sample
and a systematic review of international clinical studies
Leonardo
F. Fontenelle, Mauro V. Mendlowicz, Carla Marques and Marcio Versiani
Journal of Psychiatric Research .Volume 38, Issue 4 , July-August 2004,
Pages 403-411
Little
is known about the extent and the mechanisms through which culture may affect
the clinical manifestations of obsessive–compulsive disorder (OCD). In this
study, our objective was to identify culture-related symptomatological patterns
in OCD. We described the socio-demographic and phenomenological characteristics
of 101 adult patients with OCD seen at an university clinic for anxiety and
depressive disorders in Rio de Janeiro, Brazil, and compared them with those
reported in 15 clinical samples from North and Latin America, Europe, Africa,
and Asia identified through a systematic review in MEDLINE, PsychINFO, and
LILACS. Patients with OCD were almost universally characterized by: (1) a
predominance of females, (2) a relatively early age of onset, and (3) a
preponderance of mixed obsessions and compulsions. In contrast, a predominance
of aggressive and religious obsessions was found only in Brazilian and Middle
Eastern samples, respectively. The core features of OCD are probably relatively
independent of cultural variations. The sole exception to this rule seems to be
the content of the obsessions, in which cultural factors may play a significant
role.
Differential
patterns of psychomotor functioning in unmedicated melancholic and
nonmelancholic depressed patients
M. P. B.
I. Pier, W. Hulstijn and B. G. C. Sabbe
Journal of Psychiatric Research .Volume 38, Issue 4 , July-August 2004,
Pages 425-435
Few
studies examining psychomotor retardation (PR) in patients with major
depressive disorder (MDD) included medication-free patients. The purpose of
this study was (1) to examine whether unmedicated patients with MDD would
exhibit PR, (2) to determine whether this retardation, if present, was more
cognitive or motor in nature, and (3) to investigate whether any differences in
PR could be established between melancholic and nonmelancholic depressed
patients. Thirty-eight unmedicated inpatients with severe MDD (20 melancholic
and 18 nonmelancholic patients) and 38 matched controls were compared on figure-copying
tasks in which the cognitive task difficulty was manipulated. In addition, a
simple motor task and the symbol digit substitution task (SDST) were
administered. As a group, the patients were significantly slower performing all
tasks and both initiation times (IT) and movement times (MT) were prolonged.
However, when a distinction was made between the two subtypes, only the
melancholic patients showed prolonged MTs compared to the controls.
Furthermore, the melancholic patients differed significantly from the controls
in IT in all tasks. The nonmelancholic patients had significantly longer ITs
than the controls in two copying tasks. It can be concluded that there was
clear cognitive and motor slowing in this group of unmedicated inpatients with
MDD. The melancholic patients were more severely affected than the
nonmelancholic patients and showed a slowing of cognitive as well as motor
processes. Differences in psychomotor functioning between melancholic and
nonmelancholic depressed patients could imply different underlying
neurobiological disturbances in these subtypes of major depression.
Worsening
of depressive symptoms prior to randomization in clinical trials: a possible
screen for placebo responders?
Kenneth
R Evans, Terrence Sills, Glen R Wunderlich and Heather P McDonald
Journal of Psychiatric Research .Volume 38, Issue 4 , July-August 2004,
Pages 437-444
A common
practice in depression trials is to exclude patients whose depressive symptoms
improve between Screen and Baseline evaluations under the assumption that they
are more likely to respond to placebo.
The present
study investigated this contention by examining the relationship between
pre-randomization changes in Hamilton depression rating scale (HAMD) scores to
post-randomization placebo response and drug–placebo separation. Four
randomized, double-blind, placebo-controlled trials (active MEDICATION=fluoxetine or paroxetine)
were conducted in outpatients with Major Depressive Disorder using a novel
design in which a depressive severity inclusion criterion (HAMD 
22)
was utilized only at Screen. Patients with no change or minimal (1 point)
improvement on the HAMD between Screen and Baseline had the lowest placebo
response and the best drug–placebo separation. Patients with pre-randomization
improvement of 2 points or greater had moderately higher placebo response and
poorer drug–placebo separation. Patients who worsened between Screen and
Baseline showed the highest placebo response and the poorest drug–placebo
separation. There were no obvious differences in demographic variables between
the groups which could account for the findings. In our original analyses 3/4
studies failed to show significant drug–placebo separation. When only patients
with no change or pre-randomization improvement of 1 point were used in the
analyses, 3/4 studies showed significant drug–placebo separation while the
other study approached significance, p<0.07. These results suggest that
pre-randomization changes in HAMD scores may predict post-randomization placebo
response and drug–placebo separation. Further, pre-randomization increases in
HAMD scores (i.e., worsening) may be the best predictor of heightened placebo
responding and poor drug placebo separation.
Obsessive-compulsive
severity spectrum in the community: prevalence, comorbidity, and course
Jules Angst,
Alex Gamma, Jerome Endrass, Renee Goodwin, Vladeta Ajdacic,
Dominique Eich and Wulf Rössler
European Archives of Psychiatry and Clinical
Neuroscience 2004; Volume 254, Number 3: 156 - 164
Objectives :
To describe lifetime prevalence rates, course and
comorbidity of obsessive-compulsive disorder (OCD), obsessive-compulsive
syndromes (OCS) and OC-symptoms (OC-sx) up to age 41.
Methods :
In the Zurich community cohort study 591 subjects
were selected after screening at the age of 19 and studied prospectively by 6
interviews from 20 to 40; they represent 1599 subjects of the normal
population. The diagnoses of OCD met DSM-IV criteria.Course was assessed by
graphic illustrations and prospective data.
Results :
The lifetime prevalence rate was 3.5 % for OCD
(males 1.7%, females 5.4 %) and 8.7 % for OCS (males 9.9%, females 7.5 %). The
onset of OC-sx was 18 years (median); and in 70% before age 20.OCD was treated
in one third of cases, OCS in 6.1%. The course of symptoms was chronic in
60%,but OCD and OCS showed in most cases considerable improvements over time.
OCD reduced quality of life mostly in the subject
s
psychological wellbeing and at work but to a considerable extent also in other
social roles. Comorbidity was prominent with bipolar disorder, panic disorder
and social phobia and also significant with bulimia, binge eating, generalized
anxiety disorder and suicide attempts; there was no association with substance
abuse/dependence.
Conclusion :
OCD and OCD are manifestations of a wide spectrum
of severity with high prevalence and strong clinical validity. The long-term
course is better than generally assumed.
Tiziana
Mennini and Marco Gobbi
Life Sciences .Volume 75, Issue 9 , 16 July 2004, Pages
1021-1027
Clinical
data indicate that hydroalcoholic extracts of Hypericum perforatum might be as
valuable as conventional antidepressants in mild-to-moderate depression, with
fewer side effects. One clinical trial using two extracts with different
hyperforin contents indicated it as the main active principle responsible for
the antidepressant activity. Behavioural models in rodents confirm the
antidepressant-like effect of Hypericum extracts and also of pure hyperforin
and hypericin. A hydroalcoholic extract lacking hyperforin also lacks the antidepressant-like
effect. According to pharmacokinetic data and binding studies, it appears that
the antidepressant effect of Hypericum extract is unlikely be due to an
interaction of hypericin with central neurotransmitter receptors. The main in
vitro effects of hyperforin (at concentrations of 0.1–1 M)
are non-specific presynaptic effects, resulting in the non-selective inhibition
of the uptake of many neurotransmitters, and the interaction with dopamine D1
and opioid receptors. However, it is still not clear whether these mechanisms
can be activated in vivo, since after administration of Hypericum extract brain
concentrations of hyperforin are well below those active in vitro. In the rat,
Hypericum extract might indirectly activate sigma receptors in vivo (through
the formation of an unknown metabolite or production of an endogenous ligand),
suggesting a new target for its antidepressant effects.
Interleaved Transcranial Magnetic Stimulation/Functional
MRI Confirms that Lamotrigine Inhibits Cortical Excitability in Healthy Young
Men
Xingbao Li, Charlotte C Tenebäck,
Ziad Nahas, F Andrew Kozel, Charles Large, Jeffrey Cohn, Daryl E Bohning and
Mark S George
Neuropsychopharmacology
(2004) 29, 1395-1407
Little
is known about how lamotrigine (LTG) works within brain circuits to achieve its
clinical effects. We wished to determine whether the new technique of
interleaved transcranial magnetic stimulation (TMS)/functional magnetic
resonance imaging (fMRI) could be used to assess the effects of LTG on
activated motor or prefrontal/limbic circuits. We carried out a randomized,
double-blind, crossover trial involving two visits 1 week apart with TMS
measures of cortical excitability and blood oxygen level-dependent TMS/fMRI.
Subjects received either a single oral dose of 325 mg of LTG or placebo on each
visit. In all, 10 subjects provided a complete data set that included
interleaved TMS/fMRI measures and resting motor threshold (rMT) determinations
under both placebo and LTG conditions. A further two subjects provided only rMT
data under the two drug conditions. LTG caused a 14.9±9.6% (mean±SD) increase
in rMT 3 h after the drug, compared with a 0.6±10.9% increase 3 h after placebo
(t=3.41, df =11, p<0.01). fMRI scans showed that LTG diffusely inhibited
cortical activation induced by TMS applied over the motor cortex. In contrast,
when TMS was applied over the prefrontal cortex, LTG increased the TMS-induced
activation of limbic regions, notably the orbitofrontal cortex and hippocampus.
These results suggest that LTG, at clinically relevant serum concentrations,
has a general inhibitory effect on cortical neuronal excitability, but may have
a more complex effect on limbic circuits. Furthermore, the interleaved TMS/fMRI
technique may be a useful tool for investigating regional brain effects of
psychoactive compounds.
Heritability of
individual depressive symptoms
Kerry L.
Jang, W. John Livesley, Steven Taylor, Murray B. Stein and Erin C. Moon
Journal of Affective Disorders .Volume 80, Issues 2-3 , June 2004, Pages
125-133
Background:
In attempting to understand the familial basis of depression, most studies have
focused on broad indices of depression and mood change. Broad indices may not
adequately reflect the heritable basis of depression because of an unexplored
possibility that not all symptoms are heritable. Methods: The heritability of
individual depressive symptoms was estimated from a sample of 343 general
population volunteer twin pairs who completed the Beck Depression Inventory,
the Centre for Epidemiologic Studies Depression Scale and items from the
Symptom Checklist assessing depressive symptoms. Principal component analysis
of the items extracted 14 factors that represented a wide range of depressive
symptomatology. Results: The factors were differentially heritable (h2
range: 0.0–35.0%). The factors that have a heritable basis described endogenous
or physiological functions (e.g. loss of appetite, libido/pleasure). Symptoms
such as negative affect or tearfulness did not have a heritable basis,
suggesting that these symptoms are responses to negative life
events/experiences or a learned association to changes in physiologic function.
Limitations: Relatively small size of the sample. Conclusions: Depressive
symptoms are differentially heritable and the results suggest that future
research, such as genotyping studies, separates heritable and non-heritable
symptom clusters prior to analysis. This will help identify which genes are
involved and what their function in depression may be, leading to the
development of more targeted and effective therapies.
Residual
symptoms at remission from depression: impact on long-term outcome
N.
Kennedy and E. S. Paykel
Journal of Affective Disorders .Volume 80, Issues 2-3 , June 2004, Pages
135-144
Background:
Although residual symptoms after remission from depression are common and
predict early relapse, little is known about the impact of residual symptoms on
longer-term clinical course of depression or social functioning. Methods: Sixty
severe recurrent depressives, who remitted from an index episode of depression
with residual symptoms or below residual symptomatology, were followed-up at
8–10 years. Subjects underwent detailed longitudinal interviewing on course of
depression, treatment and socioecomonic functioning over follow-up. Results:
Long-term follow-up data was obtained on all living subjects and 55 (95%) were
interviewed. The residual symptoms group spent more time with depressive
symptoms over follow-up but not at full criteria for major depression and
showed greater impairment in longitudinal and follow-up social adjustment. No
significant differences were found between the two groups in percentage
recurring long-term, mean number of recurrences, readmissions, chronic episodes
or clinical global outcome criteria. Limitations: Long-term clinical and social
outcomes were assessed by a single retrospective longitudinal interview.
Conclusions: Patients who remit from depression with residual symptomatology
continue to have more depressive symptoms and impaired social functioning
long-term and may need more aggressive treatment.
Audrey
Millar, Colin A. Espie and Jan Scott
Journal of Affective Disorders .Volume 80, Issues 2-3 , June 2004, Pages
145-153
Background:
Several sleep laboratory studies suggest sleep abnormalities in bipolar
disorder. However, this is the first study to compare remitted bipolar subjects
with controls on actigraphic and subjective sleep parameters in a naturalistic
setting over 5 nights. Methods: Nineteen subjects with Bipolar I Disorder and
19 age- and gender-matched healthy controls were included. Objective sleep
parameters were estimated using wrist actigraphs. Subject-rated sleep diaries
and mood ratings were also completed. Sleep data were averaged for each subject
across nights, and raw score standard deviations were calculated as a measure
of within-subject variability. Results: Multivariate analyses of variance found
significant group differences for both actigraphic (F(4,33)=3.80, P=0.012) and
subjective measures (F(4,31)=3.18, P=0.027). Univariate analyses identified
reliable differences in sleep onset latency (subjective), sleep duration
(subjective), and variability of sleep duration and night wake time
(actigraphic). Binary backward stepwise logistic regression demonstrated that a
combination of three sleep measures correctly predicted disorder status in 84%
of cases. Limitations: Failure to match on sociodemographic and employment status is a
limitation that may provide an alternative explanation for some findings.
Furthermore, in the bipolar group 18 of 19 subjects were in receipt of
psychotropic medication, compared to none of the healthy control group. Also,
no information was recorded about family history of mental disorders in the
control group. Conclusions: The study suggests that the sleep of remitted
bipolar outpatients measured in naturalistic settings is characteristically
different from controls: bipolar subjects sleep longer, report longer onset
latencies, and display greater variability across nights.
Axis I and II
comorbidity in a large sample of patients with obsessive–compulsive disorder
Damiaan
Denys, Nienke Tenney, Harold J. G. M. van Megen, Femke de Geus and Herman G. M.
Westenberg
Journal of Affective Disorders .Volume 80, Issues 2-3 , June 2004, Pages
155-162
Background: No study has reported yet on the prevalence
of both comorbid DSM-IV axis I and personality disorders in a large cohort of
OCD patients, and little is known about differences in clinical characteristics
between OCD patients with and without comorbid symptoms. Objective:
To examine the cross-sectional prevalence of comorbid DSM-IV axis I, and
personality disorders in a population of patients with primary
obsessive–compulsive disorder (OCD). Method: 420 outpatients with OCD were
evaluated for comorbid pathology, demographic, and clinical characteristics. Results:
Forty-six percent of the patients were diagnosed with a comorbid disorder.
Twenty-seven percent met the criteria for at least one comorbid axis I
disorder, 15.6 percent for a comorbid personality disorder, and 20.4 percent
for both a comorbid axis I disorder and a personality disorder. Limitations:
A limitation of the current study is that the sample was drawn from a
psychiatric department specialised in anxiety disorders, which might have
underestimated the rate of comorbid diagnoses. Conclusion: Comorbid
diagnoses occur less frequently than would be expected on the basis of
comparable comorbidity studies in OCD. Associated axis I comorbidity did not
affect clinical severity of OCD, but was related to higher levels of depression
and anxiety, whereas axis II comorbidity impaired to a higher extent the
overall functioning.
A.
Negash, D. Kebede, A. Alem, Z. Melaku, N. Deyessa, T. Shibire, A. Fekadu, D.
Fekadu, L. Jacobsson and G. Kullgren
Journal of Affective Disorders .Volume 80, Issues 2-3 , June 2004, Pages 221-230
Background:
Neurological soft signs (NSS) have been reported to be more prevalent in
patients with schizophrenia compared to other psychiatric and non-psychiatric
controls. However, this issue in bipolar I disorder seems to be understudied.
Aims: The aims of the study were to examine the extent to which NSS are
associated with bipolar I disorder cases compared to healthy controls, to
assess the possible relationship between NSS and clinical dimensions of the
disorder, and to explore the association of sociodemographic characteristics
with the occurrence of NSS in cases with this disorder. Methods: Predominantly
treatment naïve cases of bipolar I disorder from rural communities were
assessed for NSS using the Neurological Evaluation Scale (NES). Results: This
study showed that patients with bipolar I disorder performed significantly
worse on two NES items from the sensory integration subscale, on one item from
motor coordination and on four items from the ‘others’ subscale, the highest
difference in performance being in items under the sequencing of complex motor
acts subscale. Clinical dimensions and sociodemographic characteristics
appeared to have no relationship with NES total score. Conclusions: Bipolar I
disorder patients seem to have more neurological dysfunction compared to
healthy controls particularly in the area of sequencing of complex motor acts.
In addition, the finding suggests that NSS in bipolar I disorder are stable
neurological abnormalities established at its onset or may be essential
characteristic features of the disorder representing stable disease process
that existed long before its onset.
Controlled
lithium discontinuation in bipolar patients with good response to long-term
lithium prophylaxis
Olcay
Yazıcı, Kaan Kora, Aslıhan Polat and Mete 
aylan
Journal of Affective Disorders .Volume 80, Issues 2-3 , June 2004, Pages
269-271
Background:
This study aims to investigate whether the risk of recurrence following lithium
discontinuation is less than reported in discontinuation of a successful,
long-term prophylaxis in bipolar patients. Methods: A total of 32 bipolar
patients discontinued lithium according to the controlled lithium
discontinuation (CLD) protocol following a definite good response to lithium
maintenance of at least 5 years. Subjects were followed for up to 9 years.
Results: The total rate of recurrence was 7% in the first week, 32% in the
first month, 62% in the first year, and 81% at the end of the 9th year following
discontinuation. Only six of the 32 patients (19%) did not have a recurrence
during the follow-up period. Conclusions: Discontinuation of lithium seems to
be followed by a high rate of recurrence in bipolar patients even after good
response to a long-duration illness-free period. A controlled discontinuation
protocol can reduce the risks of morbidity.
Cognitive-behavioral
therapy, light therapy, and their combination in treating seasonal affective
disorder
Kelly J.
Rohan, Kathryn Tierney Lindsey, Kathryn A. Roecklein and Timothy J. Lacy
Journal of Affective Disorders .Volume 80, Issues 2-3 , June 2004, Pages
273-283
Background:
The need to develop supplementary or alternative treatments for seasonal
affective disorder (SAD) is underscored by the significant minority (47%) of
SAD patients that is refractory to light therapy, the persistence of residual
symptoms despite light treatment, and poor long-term compliance with light use.
Because preliminary studies suggest that cognitive and behavioral factors are
involved in SAD, cognitive-behavioral therapy (CBT) warrants investigation as a
possible treatment option. Methods: We piloted a 6-week randomized clinical
trial to compare a standard light therapy protocol; a novel, SAD-tailored,
group CBT intervention; and their combination in ameliorating and remitting a
current SAD episode and as prophylaxis against episode recurrence. Depressive
symptom severity and remission rates were assessed at post-treatment and at a
1-year follow-up visit to examine long-term treatment durability. Results: CBT,
light therapy, and their combination all demonstrated significant reductions in
depressive symptoms on two different outcome measures. Remission rates varied
by measure, but did not reach statistical significance. During the subsequent
winter, CBT, particularly in combination with light therapy, appeared to
improve long-term outcome regarding symptom severity, remission rates, and
relapse rates. No CBT-treated participant, with or without light, experienced a
full SAD relapse compared to over 60% of those treated with light alone. Limitations:
These results should be viewed as preliminary and are limited by the small
sample size (n=23) and lack of a control group. Conclusions: The nearly half of
SAD patients who do not remit with light alone may benefit from CBT as an
adjunct or alternative treatment, especially as a prophylaxis against episode
recurrence.
Mood stabilizers: protecting the mood em leader
protecting the brain.
Brunello N.
J Affect Disord. 2004 Apr;79 Suppl:15-20.
The
mechanism underlying the therapeutic action of mood stabilizers in bipolar
disorder is not completely understood. The discovery that anticonvulsant
agents, such as valproate (VPA), were effective in the treatment of bipolar
disorder suggested a common biochemical mechanism(s) with lithium. Recent
research has focused on how VPA and lithium change the activities of cellular
signal transduction systems, especially the cyclic AMP and phosphoinositide
second messenger pathways. Despite being structurally dissimilar, VPA produces
effects on the protein kinase C (PKC) signalling pathway that are similar to
lithium, although the VPA effects appear to be largely independent of
myo-inositol. Furthermore, the therapeutic benefit of either drug require a
prolonged administration suggesting alterations at the genomic level. Studies
have revealed that both VPA and lithium altered the expression of several early
inducible genes belonging to the AP-1 family of transcription factors; this
family is responsible for controlling the expression of a number of genes
including cytoprotective proteins such as the anti-apoptotic protein, bcl-2.
Evidence shows that chronic administration of VPA or lithium can stimulate
bcl-2 expression as well as inhibit GSK-3beta activity, which renders a cell
less susceptible to apoptosis. Thus, the mood stabilizers may act to restore
the balance among aberrant signalling pathways in specific areas of the brain
and prevent degeneration.
Absolute bioavailability and absorption
characteristics of divalproex sodium extended-release tablets in healthy volunteers.
Dutta S, Reed
RC, Cavanaugh JH.
J Clin Pharmacol. 2004 Jul;44(7):737-42.
Conventional delayed-release, enteric-coated divalproex sodium tablet has an
absolute bioavailability of approximately 100%. Divalproex sodium
extended-release (ER) tablet is a novel formulation of valproic acid (VPA)
designed to release the drug slowly at a constant zero-order rate. The purpose
of this study was to evaluate the absolute bioavailability and absorption
characteristics of divalproex ER. Healthy adult volunteers (n = 16) received
divalproex ER and intravenous VPA in crossover fashion. Absolute
bioavailability was calculated as the divalproex ER/intravenous VPA ratio of
area under the curve extrapolated to infinity. The duration and rate of
absorption of VPA from divalproex ER tablets were determined by deconvolution
analysis. The geometric mean absolute bioavailability of divalproex ER was
0.896. The mean (coefficient of variation) duration of drug absorption from
divalproex ER was 21.8 (17%) hours, and the zero-order absorption rate was 21.6
(24%) mg/h for a 500-mg tablet. Divalproex ER has a lower absolute
bioavailability than conventional divalproex tablets but exhibits good
extended-release characteristics without any dose dumping.
Loci on
chromosomes 6q and 6p interact to increase susceptibility to bipolar affective
disorder in the national institute of mental health genetics initiative
pedigrees
Thomas
G. Schulze, Silvia Buervenich, Judith A. Badner, C. J. M. Steele, Sevilla D.
Detera-Wadleigh, Danielle Dick, Tatiana Foroud, Nancy J. Cox, Dean F.
MacKinnon, James B. Potash, Wade H. Berrettini, William Byerley, William
Coryell, J. Raymond DePaulo, Jr., Elliot S. Gershon, John R. Kelsoe, Melvin G.
McInnis, Dennis L. Murphy, Theodore Reich, William Scheftner, John I.
Nurnberger, Jr. and Francis J. McMahon
Biological Psychiatry .Volume 56, Issue 1 , 1 July 2004, Pages
18-23
Background
We have
reported genetic linkage between bipolar disorder and markers on chromosome
6q16.3–22.1 in the National Institute of Mental Health Genetics Initiative wave
3 pedigrees. Here we test for: 1) robustness of the linkage to differing
analysis methods, genotyping error, and gender-specific maps; 2)
parent-of-origin effects; and 3) interaction with markers within the
schizophrenia linkage region on chromosome 6p.
Methods
Members
of 245 families ascertained through a sibling pair affected with bipolar I or
schizoaffective-bipolar disorder were genotyped with 18 markers spanning
chromosome 6. Nonparametric linkage analysis was performed.
Results
Linkage
to 6q is robust to analysis method, gender-specific map differences, and
genotyping error. The locus confers a 1.4-fold increased risk. Affected
siblings share the maternal more often than the paternal chromosome (p = .006),
which could reflect a maternal parent-of-origin effect. There is a positive correlation
between family-specific linkage scores on 6q and those on 6p22.2 (r = .26; p
< .0001). Linkage analysis for each locus conditioned on evidence of linkage
to the other increases the evidence for linkage at both loci (p < .0005).
Logarithm of the odds (LOD) scores increased from 2.26 to 5.42 on 6q and from
.35 to 2.26 on 6p22.2.
Conclusions
These
results support linkage of bipolar disorder to 6q, uncover a maternal
parent-of-origin effect, and demonstrate an interaction of this locus with one
on chromosome 6p22.2, previously linked only to schizophrenia.
One-year
clinical outcomes of depressed public sector outpatients: a benchmark for
subsequent studies
A. John
Rush, Madhukar Trivedi, Thomas J. Carmody, Melanie M. Biggs, Kathy
Shores-Wilson, Hisham Ibrahim and M. Lynn Crismon
Biological Psychiatry .Volume 56, Issue 1 , 1 July 2004, Pages
46-53
Background
The
symptomatic outcomes of a cohort of public mental health sector depressed
outpatients treated for 1 year are described to provide a benchmark for future
long-term trials. Baseline moderators of outcome were evaluated.
Methods
Outpatients
with nonpsychotic major depressive disorder (n = 118) scoring ≥30 on the
30-item Inventory of Depressive Symptomatology–Clinician Rating (IDS-C30)
were treated with a medication algorithm and patient/family education package.
Response and remission rates were assessed every 3 months with the IDS-C30.
Logistic regression analyses evaluated several baseline features in relation to
outcome.
Results
While
response and remission rates increased from 3 to 12 months, the 1-year last
observation carried forward (LOCF) response (26.3%) and remission (11.0%) rates
were not impressive (sustained RESPONSE = 14.4%; sustained REMISSION = 5.1%).
Younger patients and those with full-time employment (at baseline) were more
likely to respond. A shorter length of illness tended to be associated with
higher response and remission rates (p < .10). Results are generalizable to
public sector patients with substantial socioeconomic, general medical, and
educational disadvantages who were sufficiently depressed to recommend a change
in antidepressant medication.
Conclusions
Response
and remission rates were modest when compared with outcomes in shorter duration
efficacy trials in depressed outpatients with less chronicity, fewer concurrent
general medical conditions, and less treatment resistance. Results support the
need for more powerful treatments and/or the better delivery of available
treatments.
Carlos
A. Zarate, Jr., Jennifer L. Payne, Jaskaran Singh, Jorge A. Quiroz, David A.
Luckenbaugh, Kirk D. Denicoff, Dennis S. Charney and Husseini K. Manji
Biological Psychiatry .Volume 56, Issue 1 , 1 July 2004, Pages
54-60
Background
The
original serotonergic and noradrenergic hypotheses do not fully account for the
neurobiology of depression or mechanism of action of effective antidepressants.
Research implicates a potential role of the dopaminergic system in the
pathophysiology of bipolar disorder. The current study was undertaken as a
proof of the concept that dopamine agonists will be effective in patients with
bipolar II depression.
Methods
In a
double-blind, placebo-controlled study, 21 patients with DSM-IV bipolar II
disorder, depressive phase on therapeutic levels of lithium or valproate were
randomly assigned to treatment with pramipexole (n = 10) or placebo (n = 11)
for 6 weeks. Primary efficacy was assessed by the Montgomery-Asberg Depression
Rating Scale.
Results
All
subjects except for one in each group completed the study. The analysis of
variance for total Montgomery-Asberg Depression Rating Scale scores showed a
significant treatment effect. A therapeutic response (>50% decrease in
Montgomery-Asberg Depression Rating Scale from baseline) occurred in 60% of
patients taking pramipexole and 9% taking placebo (p = .02). One subject on
pramipexole and two on placebo developed hypomanic symptoms.
Conclusions
The
dopamine agonist pramipexole was found to have significant antidepressant
effects in patients with bipolar II depression.
Do
stressful life-events or sociodemographic variables associate with depression
and alexithymia among a general population?—a 3-year follow-up study
Kirsi
Honkalampi, Heli Koivumaa-Honkanen, Jukka Hintikka, Risto Antikainen, Kaisa
Haatainen, Antti Tanskanen and Heimo Viinamäki
Comprehensive Psychiatry .Volume 45, Issue 4 , July-August 2004,
Pages 254-260
This
3-year follow-up study examined background factors, stressful life-events, and
changes in alexithymia and depression scores in four groups of subjects from a
general population (N = 1,339): alexithymic (A), depressed (D), simultaneously
alexithymic/depressed (AD), and non-alexithymic/non-depressed (O). Alexithymia
was assessed using the 20-item version of the Toronto Alexithymia Scale (TAS)
and depression using the 21-item Beck Depression Inventory (BDI). A
questionnaire screening sociodemography and stressful life-events was also
used. The results showed that alexithymia was associated with male gender and
blue-collar working, whereas depressive symptoms associated with female gender,
older age, poor subjective health, poor financial situation, and low life
satisfaction. During the follow-up the sum of stressful life-events was higher
among groups AD and D than in groups A and O. The most common stressful
life-events were the death of a close relative or friend, a negative change in
the health of a family member, and financial problems. The TAS scores decreased
only in groups A and AD. The BDI scores decreased in group AD but remained
relatively unchanged in group D. Interestingly, if only those without
depressive symptoms are considered, alexithymia appears to be a rarer
phenomenon than has been reported previously. Furthermore, it seems that depressive
symptoms were chronic and long-lasting among the general population.
Adjustment to antidepressant utilization rates to
account for depression in remission
Cynthia
A. Beck and Scott B. Patten
Comprehensive Psychiatry .Volume 45, Issue 4 , July-August 2004,
Pages 268-274
Conventional estimates of antidepressant
(AD) utilization in major depressive syndrome (MDS) have been low, but this may
be partially because ongoing AD use by individuals with resolved MDS is not
included. Valid estimates of AD utilization should include this ongoing use for
MDS, but this is difficult since most surveys do not collect data on the reason
for taking ADs. Only a proportion (fdep) of the nondepressed (nMDS)
population taking ADs does so for depression. Published studies have not
reported this proportion, and data required to estimate fdep are not
usually available from surveys. The current study was performed to (1) estimate
fdep by employing information on past history of depression, and (2)
use the estimate to obtain an "adjusted" AD utilization rate,
including resolved MDS subjects taking ADs. Data were collected in Calgary in
1998 and 1999 by random-digit dial telephone interview from consenting adults
aged 18+ years. MDS was assessed using the Composite International Diagnostic
Interview Short Form for Major Depression (CIDI-SFMD). Data were gathered on
current medications, past depression, and current chronic physical illness. Of
2,542 respondents, 17.1% had MDS as defined by the CIDI-SFMD. A total of 20.2%
of MDS and 3.2% of nMDS subjects were taking ADs. Of nMDS individuals taking ADs,
70.6% reported past depression (fdep = 70.6%). An
"adjusted" AD utilization rate including this group was 28.2%.
Physical illnesses that can be treated with ADs affected only 30.0% of nMDS
subjects without past depression taking ADs. This study suggests that most
individuals without active depression taking ADs do so for depression. AD
utilization rates that ignore this group may be unrealistically low. AD use
among nMDS subjects without previous depression is probably not primarily for
physical illnesses. Limitations include the use of a brief predictive
instrument for MDS, and self-report of past depression.
Peter R. Joyce ; Suzanne
E. Luty ; Janice M. McKenzie ; Roger T. Mulder ; Virginia V. McIntosh ; Frances
A. Carter ; Cynthia M. Bulik ; Patrick F. Sullivan
Australian and New Zealand Journal
of Psychiatry 2004; Volume: 38 Number: 6 Page: 433 -- 438
Objective:
To compare the personality traits and disorders of patients with bipolar II
disorder and major depression and to examine the impact on treatment outcome of
a bipolar II diagnosis. Method:
Patients from two clinical trials, a depressive sample (n = 195, 10% bipolar
II) and a bulimic sample (n = 135, 16% bipolar II), were assessed for
personality traits using DSM-IV criteria. Patients were randomised to
treatments (fluoxetine or nortriptyline for depressive sample; cognitive
behaviour therapy for bulimic sample) and followed for 3 years (depressive
sample) or 5 years (bulimic sample) to assess the impact on outcome of a
bipolar II diagnosis. Results:
Bipolar II patients were assessed as having more borderline, histrionic and
schizotypal personality traits than patients with major depression. A baseline
bipolar II diagnosis did not impact negatively on treatment outcome, and less
than 5% of bipolar II patients developed bipolar I disorder during follow up.
Conclusions:
The low rate of conversion of bipolar II to bipolar I disorder and the lack of
adverse impact of the diagnosis on outcome, questions the need for antimanic or
mood stabliser medication in most bipolar II patients.
Length of therapy with selective serotonin reuptake
inhibitors and tricyclic antidepressants in Australia
Peter McManus ; Andrea
Mant ; Philip Mitchell ; John Dudley
Australian and New Zealand Journal
of Psychiatry 2004; Volume: 38 Number: 6 Page: 450 -- 454
Objective:
To investigate the proportion of patients starting on either selective
serotonin reuptake inhibitors (SSRIs) or tricyclic antidepressants (TCAs) who
continued treatment for a period consistent with recommended guidelines for
major depression, that is at least 6 months. Method:
Cohort study using a national dispensing claims database involving patients
eligible for social security entitlements in Australia. Two 'new user' cohorts
were established of patients who were supplied a prescription for either an
SSRI (6026) or a TCA (4158) in the first week of April 2000 and who had not
received a prescription for any antidepressant in the preceding three months.
The main outcome measure was the proportion of patients who were still having
any SSRI or TCA prescription, respectively, dispensed between 6 and 8 months
after initiation. Additionally, for patients starting on either a leading SSRI
(sertraline) or TCA (dothiepin), the proportions of those that remained on
these drugs or had changed to other antidepressants were determined. The
dispensing data are not linked to reason for prescribing in the national
dataset. Results:
2267 SSRI 'new users' (38%) were still receiving SSRIs 6-8 months later,
compared with 1269 (31%) of the 4158 TCA 'new users' (p < 0.001). The
difference between the groups occurred early, by the 2-4 month time interval.
1038 (41%) of patients starting on the individual SSRI and 385 (38%) of patients
starting on the individual TCA were receiving some type of antidepressant
therapy at 6-8 months, with no significant difference (p = 0.6) in the
proportions that had changed to another antidepressant. Conclusions:
In 2000, only 40% of patients started on an antidepressant continued to be
prescribed some antidepressant therapy 6-8 months later. Patients were more
likely to continue on SSRIs as a class than on TCAs and the difference in
continuation between these two classes occurred within the first 2 months of
therapy. However, patients starting on an individual SSRI or TCA were equally
likely to change to another antidepressant.
Alprazolam
extended-release in panic disorder
Karl Rickels
Expert Opinion on Pharmacotherapy .2004,
vol. 5, no. 7, pp. 1599 - 1611
Alprazolam-XR
is an extended-release formulation of alprazolam designed to
deliver sustained therapeutic concentrations for 24 h after once-daily dosing.
Plasma concentrations gradually decline as the time for the next dose
approaches, but still remain above therapeutic minimum levels. The anti-panic
efficacy of alprazolam-XR appears to
be comparable to the original formulation of alprazolam. The main
advantage of the new extended-release formulation appears to be its greater
tolerability and safety. The speed with which high-potency benzodiazepines are
absorbed, and rise to peak concentrations is correlated with both abuse
potential and with the incidence and severity of common adverse events, such as
sedation and cognitive and psychomotor impairment. Alprazolam-XR does not
exhibit the sudden increases in plasma concentration characteristic of the
original formulation of alprazolam.
This pharmacokinetic difference appears to translate into a reduced liability
of abuse and a reduced incidence of sedation and cognitive and psychomotor
impairment during acute therapy. This would appear to give alprazolam-XR a more favourable
benefit:risk profile than the original formulation of alprazolam. In addition,
the once-daily dosing (as opposed to three or four times per day) reduces
clock-watching, increases compliance and it eliminates the penalty of
breakthrough anxiety and panic that many patients experience if they
inadvertently miss a dose. It should be noted that long-term therapy with alprazolam-XR carries the
same risk of dependence and withdrawal during discontinuation as the original
formulation of alprazolam.
Frederico
G. Graeff
Neuroscience & Biobehavioral Reviews .Volume 28, Issue 3 , May 2004, Pages
239-259
This article
reviews experimental evidence and theoretical constructs that implicate
serotonin (5-HT) modulation of defensive behavior within the midbrain
periaqueductal gray in panic disorder (PD). Evidence with conflict tests in
experimental animals indicates that 5-HT enhances anxiety, whereas results with
aversive stimulation of the dorsal periaqueductal gray point to an anxiolytic
role of 5-HT. To solve this contradiction, it has been suggested that the
emotional states determined by the two types of animal model are different. Conflict
tests would generate conditioned anxiety, whereas periaqueductal gray
stimulation would produce unconditioned fear, as evoked by proximal threat.
Clinically, the former would be related to generalized anxiety while the latter
to PD. Thus, 5-HT is supposed to facilitate anxiety, but to inhibit panic. This
hypothesis has been tested in the animal model of anxiety and panic named the
elevated T-maze, in two procedures of human experimental anxiety applied to
healthy volunteers or panic patients, and in CO2-induced panic
attacks. Overall, the obtained results have shown that drugs that enhance 5-HT function increase
different indexes of anxiety, but decrease indexes of panic. Drugs that impair 5-HT function have the
opposite effects. Thus, so far the predictions derived from the above
hypothesis have been fulfilled.
D. M.
Bannerman, J. N. P. Rawlins, S. B. McHugh, R. M. J. Deacon, B. K. Yee, T. Bast,
W. -N. Zhang, H. H. J. Pothuizen and J. Feldon
Neuroscience & Biobehavioral Reviews .Volume 28, Issue 3 , May 2004, Pages
273-283
The amnestic
effects of hippocampal lesions are well documented, leading to numerous
memory-based theories of hippocampal function. It is debatable, however,
whether any one of these theories can satisfactorily account for all the
consequences of hippocampal damage: Hippocampal lesions also result in
behavioural disinhibition and reduced anxiety. A growing number of studies now
suggest that these diverse behavioural effects may be associated with different
hippocampal subregions. There is evidence for at least two distinct functional
domains, although recent neuroanatomical studies suggest this may be an
underestimate. Selective lesion studies show that the hippocampus is
functionally subdivided along the septotemporal axis into dorsal and ventral
regions, each associated with a distinct set of behaviours. Dorsal hippocampus
has a preferential role in certain forms of learning and memory, notably
spatial learning, but ventral hippocampus may have a preferential role in brain
processes associated with anxiety-related behaviours. The latter's role in
emotional processing is also distinct from that of the amygdala, which is
associated specifically with fear. Gray and McNaughton's theory can in
principle incorporate these
apparently distinct hippocampal functions, and provides a plausible unitary
account for the multiple facets of hippocampal function.