FORUM ON MOOD
AND ANXIETY DISORDERS
Monte-Carlo, November 28 - December 1, 2001
I - M
Albert, C. Bergesio, F. Bogetto
Aim of the study Phobias, including pharmacophobia, are an inherent
feature of Panic Disorder (PD); moreover, PD patients are especially
sensitive to physical symptoms and medication side effects. These essential
features of PD exert a negative influence on the compliance of patients to
the pharmacological therapy, especially at the beginning of the treatment.
The aim of the present study was to investigate compliance to
pharmacological treatment and drop‑out rates due to severe adverse
events at the beginning of therapy in a group of patients with PD, and
compare them to those of a control group of patients suffering from OCD.
Materials and Methods 198 patients with a principal diagnosis of PD (DSM-IV)
entered a 12-week acute treatment period with SSRIs. Target doses and time
to reach the target dose followed the APA Treatment Guidelines for Panic
Disorder. Patients were assessed weekly during the first 4 weeks in order to
evaluate compliance and drop-out rates due to adverse events. For the
purposes of the present study patients were considered poor-compliant
whenever they skipped a drug dose. During the first 4 weeks patients
received medication from the study staff and were instructed to return all
drug packaging to the study site in order to allow drug accountability.
Adverse events were recorded using the UKU Side Effect Scale;
drop‑outs due to side effects were recorded. Poor‑compliance and
drop-out rates were compared to those of a group of 198 patients with a principal diagnosis of OCD matched for age and
sex and treated with SSRIs according to international treatment guidelines.
The chi-square test was used for statistical comparisons.
Results The rate of poor-compliance
at the end of the first 4 weeks of treatment was 24.2% for PD patients;
10.6% of patients discontinued before the fourth week because of adverse
events. When examining gender-differences, a significant difference emerged
only for drop-out rates, with males discontinuing significantly more than
females (16.9% vs. 7.1 %). OCD subjects showed a poor‑compliance rate
significantly lower that that reported for PD patients (10.7% vs. 24.2%);
this significant difference was mainly due to the difference between PD
females and 0CD females (26.8% vs. 5.4%). No differences between PD and OCD
patients were detected with regard to drop‑out rates due to side
results confirm that 1) PD patients have a higher poor‑compliance rate
compared to OCD patients; this difference is even stronger for females; we
might speculate that this high poor-compliance rate is due to
pharmacophobia; 2) drop out rates during the first 4 weeks of treatment are
not higher in PD patients than in OCD subjects. This might indicate that PD
patients, once they get treatment, do not report more severe adverse events
as compared to other anxiety disorder subjects.
TO FULL WORK FUNCTION WITH TREATMENT OF DEPRESSION
J Chen, R Entsuah
The study objective was to evaluate baseline [BL] impairment in work
and corresponding improvement following treatment of depression.
Data from 8 clinical studies of 2046 patients meeting DSM-III-R or
DSM-IV criteria for moderate-severe depressive disorder were pooled.
Patients were randomly assigned to receive venlafaxine/venlafaxine XR
[VEN/VEN XR] 75–375 mg/d (n=851); a selective serotonin reuptake inhibitor
[SSRI] (fluoxetine, paroxetine, or fluvoxamine at various dosages, n=749);
or placebo (n=446). Work and Activities (WA) item scores (0 to 4) were
evaluated at BL and after 8 weeks of treatment. Of patients who were
completely impaired (WA item score 4) at BL, the proportion who had improved
to full work functionality (WA item score 0) was compared across treatment
At BL, median WA item score for all patients was 3. Overall, 15%
(312/2046) had a BL score of 4; the placebo group had significantly fewer
patients with complete work impairment (9.6% compared with 16.0% for the
SSRI group and 17.5% for the VEN/VEN XR group). After 8 weeks’ treatment,
28.9% (43/149) of patients who were completely impaired in the VEN/VEN XR
group had improved to full functionality compared with 15.8% (19/120) of
patients in the SSRI group (VEN/VEN XR/SSRI OR=2.2, P=0.01)
and 16.3% (7/43) of patients in the placebo group (VEN/VEN XR/placebo
OR=2.1, P=0.11; SSRI/placebo OR=0.97, P=1.0).
A significant proportion of patients who were completely work impaired at BL improved dramatically to full functionality by treatment end. VEN/VEN XR was associated with the highest proportion of such dramatically improved patients.
In patients with major depressive disorder, we
compared the effect of venlafaxine, SSRIs, and placebo on specific
depressive symptoms and patient characteristics predictive of work
impairment and of improvement with treatment.
Data were pooled from 8 clinical studies of 2046 intent-to-treat patients
meeting DSM-III-R or -IV
criteria for moderate-to-severe depression given venlafaxine (75–375
mg/d), an SSRI (fluoxetine, paroxetine, or fluvoxamine at various dosages),
or placebo. Work impairment was measured using the Work and Activities (WA)
item of the HAM-D17. Logistic regression identified
the baseline characteristics significantly (at p<0.05) predictive of behavioral work
impairment (WA=3 or 4) at baseline.
At baseline, 76% of patients were behaviorally work impaired; 15%
had ceased employment (WA=4). Moderate-to-severe CGI‑S scores,
above-average baseline retardation, general somatic symptoms, genital
symptoms, late insomnia, and above-average age were significantly predictive
of behavioral work impairment at baseline. Patients with above-average
baseline retardation and suicidality, work dysfunction, and above-average
age were significantly less likely to attain early, sustained return to full
work function; those with a longer-than-average depressive episode and those
treated with venlafaxine were significantly more likely to do so.
The finding that a longer depressive episode increased the odds of a sustained return to full work function may represent successful spontaneous coping over time unrelated to treatment. However, treatment with venlafaxine was independently predictive of enabling patients with severe baseline depressive symptoms and work dysfunction to return earlier to sustained full work function, in relation to both SSRIs and placebo.
OF U-50,488H, A KAPPA-OPIOID RECEPTOR AGONIST, ON THE LEARNED HELPLESSNESS
MODEL OF DEPRESSION IN MICE.
M. Suzuki and M. Ukai
of Chemical Pharmacology, Faculty of Pharmacy, Meijo University, Yagotoyama,
150, Tempaku-ku, Nagoya, 468-8503, JAPAN
helplessness is widely employed as a model of depression with high validity
criteria. Several pharmacological and neurochemical findings support a
role for opioid systems in affective disorders in the experimental and
clinical studies. Because it is
unknown whether kappa-opioid receptor agonist is involved in the learned
helplessness model of depression, in this study we evaluate the effects of
U-50,488H on learned helplessness in mice.
albino ddY mice (5-8 weeks old) were used.
1. Inescapable electric
shock pretreatment: Mice were
treated with inescapable electric footshocks.
Conditioned avoidance response:
Active conditioned avoidance response was observed 24 h after
inescapable electric shock. Each
animal was placed singly in the box and subjected to 30 active conditioned
avoidance training. To avoid
the electric shock, the mouse had to press the lever in the box.
An escape failure was considered when the mouse failed to escape the
shock. Active conditioned
avoidance training were performed for 4 consecutive days, and the number of
escape failures was recorded. All
experiments were performed in accordance with the Guidelines for Animal
Experiments of Meijo University.
saline-treated animals displayed fewer escape failures than shocked animals.
Mice pre-exposed to inescapable electric shocks were treated with
U-50,488H. Stimulation of kappa
-opioid receptors by U-50,488H (10 mg/kg i.p.) attenuated the escape
failures induced by shock pre-exposure.
This improvement by U-50,488H was blocked by MR2266, an opioid
receptor antagonist. Although
the precise nature of the interaction in the kappa -opioid systems of the
brain is unknown, kappa -opioid receptor agonists may activate the impaired
neuronal systems. These results
suggest that kappa-opioid receptor agonist plays an inhibitory role in the
learned helplessness in mice.
This study was supported in part by Grants-in-Aid for Scientific
Research and Scientific Frontier Research Project from Ministry of
Education, Culture, Sports, Science and Technology, Japan.
AND LIFETIME PANIC DISORDER COMORBIDITY IN BIPOLAR I DISORDER WITH PSYCHOTIC
Mastrocinque, S. Pini, L. Dell’Osso, S. Navari, M. Morandi, N.
Mosti, M. Abelli, G.B. Cassano
Objective: Bipolar I disorder often co-occurs with panic disorder,
but little is known about the relationships between the clinical features of
bipolar illness and this comorbid condition. The authors assessed comorbid
lifetime and current axis I panic disorder
in 166 patients with bipolar I disorder with psychotic features and
the relationships of this comorbid disorder to selected clinical and
historical illness variables.
Method: 166 outpatients with bipolar I
disorder with psychotic features were evaluated using structured diagnostic
interviews and clinician-administered and self-rated questionnaires to
determine the diagnosis of bipolar disorder, comorbid axis I disorder
diagnoses, and demographic and clinical characteristics.
Results: Of the 166 bipolar patients, 34
(20.5%) fulfilled DSM-IV criteria for lifetime diagnosis of panic disorder
(no panic attacks during the month previous to the evaluation), 17 (10.2%)
for current panic disorder (panic attacks during the last month) and
115 (69.3%) had no panic disorder comorbidity. Comparisons among
these three groups showed that the group with lifetime panic disorder
comorbidity had an earlier age at onset of syndromal bipolar disorder,
higher levels of phobic anxiety and more frequent depressive polarity at the
index episode. Current axis I panic comorbidity was associated with a
history of substance abuse, more severe thought disturbances and activation
and more frequent mixed polarity at index episode, this latter reaching
borderline statistical significance.
Conclusions: Patients with bipolar
disorder with psychotic features often have comorbid panic disorder.
Consideration of both lifetime and current axis I panic disorder comorbidity
in bipolar disorder might represent a clinically useful way of
characterizing or subtyping the illness. Further research into the
prognostic and treatment response implications of panic disorder comorbidity
in bipolar disorder is important.
WITH RISPERIDONE AND OLANZAPINE IN BIPOLAR DISORDER
Mehnert (1), M
Jones (2), L Fellows (3). On Behalf of the RODOS Investigator Group.
Janssen Research Foundation, Beerse, Belgium; (2) Department of Psychology,
Macquarie University, Sydney, Australia; (3) Graylands Selby-Lemnos and
Special Care Health Services, Mount Claremont, Western Australia.
Objective: To compare the patterns of drug usage,
costs and outcomes associated with the inpatient treatment of bipolar
disorder with risperidone (RIS) or olanzapine (OLA).
A retrospective cohort study using patient chart review was undertaken.
Patients were included if the following inclusion criteria were fulfilled:
(1) diagnosis of bipolar disorder, (2) discharged or at least 120 days of
follow-up, (3) £
65 years of age and (4) treated with either RIS or OLA. Treatment outcomes
and cost of treatments were calculated and statistically analysed.
Results: Data on 62 patients was available (RIS=30, OLA=32) from hospitals in Australia, The Netherlands, Norway and Spain. Demographic characteristics for the two samples were similar. The median time to onset of efficacy was 9 days for RIS and 12 days for OLA. The average daily dose for RIS was 3.0 ± 1.5mg and with OLA 11.0 ± 4.1mg. Tolerability of study drugs was generally good in both groups, with 10% of RIS-treated and 16% of OLA-treated patients discontinuing therapy. Patients receiving OLA were more likely to discontinue due to lack of efficacy (9%) than those receiving RIS (0%), although this difference did not reach statistical significance (p=0.09). Usage of concomitant neuroleptics and other medications was similar in the two groups. Daily costs of the studied medication were over twice as high for OLA (4.6 ± 1.7 USD) than for RIS (2.0 ± 1.0 USD, p<0.0001). Daily costs for all in-patient drug use were also significantly higher in the OLA group (6.2 ± 2.4 USD) than the RIS group (2.9 ± 1.9 USD, p<0.0001).
Conclusions: RIS and OLA were both effective in the bipolar patients studied. In-patient costs for patients receiving RIS were significantly lower than costs for patients receiving OLA in this sample of patients with bipolar disorder.
OUTCOMES WITH ATYPICAL
ANTIPSYCHOTICS IN SCHIZOPHRENIA AND MOOD DISORDER
Mehnert (1), M
Jones (2), L Fellows (3). On Behalf of the RODOS Investigator Group. (1)
Janssen Research Foundation, Beerse, Belgium; (2) Department of Psychology,
Macquarie University, Sydney, Australia; (3) Graylands Selby-Lemnos and Special Care Health
Services, Mount Claremont, Western Australia.
Objective: To compare the outcomes
associated with atypical antipsychotic treatment in patients with
schizophrenia and mood disorder.
Methods: A retrospective cohort study using patient chart review was undertaken. Patients were included if the following inclusion criteria were fulfilled: (1) diagnosis of schizophrenia or mood disorder, (2) discharged or at least 120 days of follow-up, (3)£ 65 years of age, (4) treated with either risperidone (RIS) or olanzapine (OLA).
Results: Data on 1901 patients with schizophrenia and 112 patients
with mood disorders were available from hospitals in 9 countries: Australia,
Austria, Denmark, Germany, Great Britain, The Netherlands, Norway, Spain and
Sweden. Schizophrenia patients typically had an earlier age of onset of
symptoms (24.5 years) than those with mood disorder (30.1 years, p=0.0002).
Patients with mood disorder received lower doses of RIS or OLA
(p<0.0001), and were more often discharged within 120 days (p=0.02). A
slightly shorter time to achieve efficacy (10 days versus 12 days) was seen
in patients with mood disorders (p=0.01). Median time to discharge was
significantly shorter in patients with mood disorders (22 days) than
patients with schizophrenia (35 days, p<0.0001). Adjusting for background
factors has little impact on the dose comparison, time-to discharge or
time-to efficacy analyses.
Conclusions: Atypical antipsychotics were effective in treating acute
psychotic exacerbations in schizophrenia and mood disorders, with a median
time to efficacy of 10-12 days. Patients with mood disorders generally
required lower doses of atypical antipsychotic and were discharged faster
than schizophrenic patients.
OF LIFE IMPROVEMENTS UPON SWITCHING PATIENTS FROM