Obsessive-compulsive disorder in hospitalized patients with chronic schizophrenia.

Obsessive-compulsive (OC) symptoms have been observed in a substantial proportion of schizophrenic patients. In this study, we assessed the rate of occurrence of OC symptoms and the interrelationship between OC and schizophrenic symptoms in 68 hospitalized chronic schizophrenic patients. The patients were interviewed with the Structured Clinical Interview for Axis-I DSM-IV Disorders - Patient Edition (SCID-P) and the appropriate rating scales including the Scale for the Assessment of Positive Symptoms, the Scale for the Assessment of Negative Symptoms, the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), the Barnes Akathisia Scale, the Abnormal Involuntary Movement Scale, and the Social Behaviour Schedule (SBS). Sixteen patients (23.5%) met the DSM-IV criteria for OCD. A comparison of schizophrenic patients with and without OCD showed that the schizo-obsessive patients were significantly (1.7-fold) more impaired in basic social functioning, as reflected by the SBS score. No significant between-group differences for any of the other clinical variables were found. There was no significant correlation between OC and schizophrenic symptoms within the schizo-obsessive subgroup. The mean Y-BOCS score for the patients with both schizophrenia and OCD was within the typical range (22.8+/-1.7) observed in OCD without psychosis. The findings provide further evidence for the importance of the OC dimension in schizophrenia and may have important implications for the application of effective treatment approaches in this difficult-to-treat subgroup of schizophrenic patients.

Evidence for the effectiveness of olanzapine among patients nonresponsive and/or intolerant to risperidone.

BACKGROUND: This multicenter, open-label study evaluated the efficacy and safety of olanzapine in patients with schizophrenia who had been nonresponsive or intolerant to a course of risperidone (mean duration of risperidone treatment = 46.3 days). METHOD: A total of 34 patients with DSM-III-R and ICD-9 schizophrenia entered this trial. Twenty-five patients were nonresponsive to previous risperidone treatment, 6 patients were intolerant to the risperidone treatment, and 3 patients listed both reasons for discontinuation of risperidone. Patients were treated across a dose range of 5 to 25 mg/day of olanzapine. The primary efficacy variable was baseline to endpoint change in Positive and Negative Syndrome Scale (PANSS) score. Safety was assessed using the Clinical Global Impressions-Severity of Illness scale. RESULTS: Improvement from baseline PANSS score (mean +/- SD PANSS score = 119.4 +/- 26.9) was evident at the week-6 midpoint (-22.2 +/- 19.5) and at the week-14 endpoint (-28.7 +/- 22.3). On average, severity ratings were reduced from baseline by 25% after 14 weeks of olanzapine therapy. Twenty olanzapine-treated patients (58.8%) achieved the a priori-defined response criterion of > or = 20% reduction in PANSS total score. Among patients who met the response criterion, 50% (10/20) had done so by the fourth week. These clinical improvements occurred across a broad range of symptom domains and included reductions in PANSS positive, negative, general psychopathology, and mood subscores. No statistically significant differences were found on any efficacy measure at any visit between the patients who were nonresponsive to risperidone compared with those who were intolerant to risperidone. Olanzapine was well tolerated, with no subject discontinuing early owing to an intolerable adverse event that could be conclusively linked to olanzapine. CONCLUSION: The results of this open-label study suggest that olanzapine may be an effective alternative for schizophrenic patients who are nonresponsive and/or intolerant to risperidone treatment. Moreover, the results underscore the differential pharmacology that exists among the newer antipsychotic agents.

The effectiveness of olanzapine in treatment-refractory schizophrenia when patients are nonresponsive to or unable to tolerate clozapine.

OBJECTIVE: This multicenter, open-label study was designed to assess the efficacy and tolerability of olanzapine in patients with chronic schizophrenia who are resistant to therapy with classic neuroleptic agents and are either not responsive to or unable to tolerate clozapine. METHODS: Patients received olanzapine orally once daily for 18 weeks at doses ranging from 5 to 25 mg. The primary efficacy measure was change in the total score on the Positive and Negative Syndrome Scale (PANSS) from baseline to end point. Secondary efficacy measures were the total score on the Brief Psychiatric Rating Scale (BPRS); the PANSS positive, negative, general psychopathology, and mood subscores; and the Clinical Global Impression improvement score. Also recorded were spontaneously reported adverse events; extrapyramidal symptoms (assessed by the Abnormal Involuntary Movement Scale, Simpson-Angus Scale, and Barnes Akathisia Scale); vital signs; and clinical laboratory test results. RESULTS: Forty-eight patients were treated with olanzapine; of these, 45 were assessable over the full 18-week study period. Total scores on the PANSS and BPRS were reduced from baseline by an average of 17.7 (14.2%) and 9.8 points (20.2%), respectively. Eighteen patients (40.0%) experienced a treatment response, defined as a reduction in PANSS total score of > or = 20%. A total of 25 patients (55.6%) achieved a similar reduction in BPRS total score. Significant reductions were seen in both the positive and negative symptom scores on the PANSS (P < 0.001). Olanzapine was well tolerated, with minimal treatment-emergent adverse events or clinically relevant changes in vital signs or clinical laboratory test results. No clinically significant blood dyscrasias were observed in olanzapine-treated patients, including those who had discontinued clozapine because of treatment-associated leukopenia or neutropenia. CONCLUSION: The results of this study suggest that olanzapine may be of benefit in patients who are refractory to or unable to tolerate clozapine.

Actigraphic monitoring (actigraphy) of circadian locomotor activity in schizophrenic patients with acute neuroleptic-induced akathisia.

BACKGROUND: Actigraphy is a quantitative method for measurement of motor activity. In the present study we used actigraphy to examine diurnal variations in locomotor activity of schizophrenic patients with neuroleptic-induced akathisia (NIA). METHOD: Thirty-two schizophrenic patients, 16 with NIA and 16 without (DSM-IV criteria) underwent 24-h actigraphic monitoring. Clinical assessments of NIA were conducted with Barnes Akathisia Scale (BAS) at 08:00, 12:00, 16:00 and 20:00. Sleep parameters (duration, latency, continuity and efficacy) were assessed by actigraphy. Sleep quality was evaluated by a self-rated sleep questionnaire. RESULTS: NIA patients demonstrated persistent higher daytime motor activity from 11:30 to 14:15 and from 18:00 to 21:00 than controls. There were no differences between the groups in nighttime motor activity, confirming clinical observations that NIA tends to disappear during sleep. Subject's sleep assessments were similar in the two groups. CONCLUSIONS: Actigraphy seems to be a reliable, non-invasive, method of measuring motor activity in patients with NIA. Its sensitivity and specificity as an objective quantitative diagnostic instrument in patients with NIA merits further investigation.

Association of unipolar major depressive disorder with genes of the serotonergic and dopaminergic pathways.

Major depressive disorder (MDD) is a severe psychiatric disorder with a lifetime prevalence of about 15%.1 The importance of the genetic component is well accepted,2 but the mode of inheritance is complex and non-Mendelian. A line of evidence suggests the involvement of serotonin and dopamine neurotransmitters in the pathophysiology of depression. In the present study, 102 unipolar MDD patients and 172 healthy controls were genotyped for polymorphisms in four serotonergic and three dopaminergic candidate genes [tryptophan hydroxylase (TPH), serotonin receptor 2A (HTR2A), serotonin receptor 2C (HTR2C), serotonin transporter promoter region (5-HTTLPR), dopamine receptor D4 (DRD4), dopamine transporter (DAT1) and catechol-O-methyl transferase (COMT)]. There were no statistical differences between MDD patients and healthy controls in the genotypic and allelic distribution of all polymorphisms investigated. Thus, our study does not support a major role for these polymorphisms in contributing to susceptibility to MDD, although it does not preclude minor effects.

Treatment of neuroleptic-induced akathisia with the 5-HT2 antagonist mianserin. Double-blind, placebo-controlled study.

BACKGROUND: Serotonin (5-HT):dopamine imbalance may underlie neuroleptic-induced akathisia. AIM: To evaluate the efficacy of the 5-HT2 antagonist, mianserin in neuroleptic-induced akathisia. METHODS: Thirty neuroleptic-treated patients with schizophrenia were randomly allocated in a double-blind design to receive either mianserin (15 mg/day) or placebo for five days. Patients were assessed at baseline and on Days 3 and 5 by the Barnes Akathisia Scale (BARS), as well as by other relevant clinical rating scales. RESULTS: Compared with the placebo group, the mianserin-treated patients showed a significant reduction in all four BARS subscales by Day 5, with mean reductions in the BARS global score of 9.9% and 52.2%, respectively (P = 0.006). Response to treatment (a reduction of at least two points on the BARS global subscale), was noted in six patients (40%) in the mianserin group and only one patient (9.1%) in the placebo group (P = 0.04, log odds ratio 2.23). CONCLUSIONS: Mianserin at a low dose may be a promising therapeutic option for patients with acute neuroleptic-induced akathisia.

Fluvoxamine treatment of obsessive-compulsive symptoms in schizophrenic patients: an add-on open study.

Obsessive-Compulsive (OC) symptoms are observed in a substantial proportion of schizophrenic patients and pose a significant therapeutic challenge. Based on findings of the benefit of the anti-obsessive agent clomipramine, we designed an open-label study to examine the effect of adding the serotonin-selective reuptake inhibitor (SSRI) fluvoxamine to the ongoing antipsychotic regimen of schizo-obsessive patients. The study population consisted of ten neuroleptic-stabilized chronic schizophrenic patients with OC symptoms. Fluvoxamine (up to 150 mg/day) was added to the ongoing antipsychotic treatment, which remained unchanged for the entire 12-week trial period. The patients were evaluated before the trial and at weeks 1, 2, 4, 6, 8 and 12 (end point) with the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), the Schedule for Assessment of Positive Symptoms and the Schedule for Assessment of Negative Symptoms. The results showed a significant improvement in obsessions (P < 0.02) (but not compulsions) and both positive (P < 0.01) and negative (P < 0.05) schizophrenic symptoms. By the end of the trial, three patients showed a more than 50% reduction in the Y-BOCS score, with complete amelioration of the OC symptoms in one of them. Three patients were dropped from the study during the first 4 weeks, two because of aggressiveness and one because of psychotic exacerbation. No exacerbation or new onset of extrapyramidal side-effects (EPS), as measured by the Barnes Akathisia Scale (BARS) and the Simpson-Angus Scale (SAS), was noted during the course of the trial and there were no other significant clinical side-effects of fluvoxamine addition. We conclude that fluvoxamine may be an effective adjunctive agent in some schizo-obsessive patients.

Emergence of obsessive--compulsive symptoms and tics during clozapine withdrawal.

Treatment with clozapine may be associated with the appearance of obsessive-compulsive (OC) symptoms in up to 10% of schizophrenic patients. We present the first report of the emergence of de novo OC symptoms during clozapine withdrawal in two schizophrenic patients, associated in one with Tourette's syndrome-like tics. Resumption of clozapine led to the complete disappearance of the OC symptoms and a substantial alleviation of the tics. It is suggested that an imbalance between the dopamine and serotonin systems may account for this complication.

Akathisia-like behavior following ECT, and its successful treatment with low-dose mianserin.

The development of akathisia-like behavior during a course of electroconvulsive therapy (ECT) in a patient with psychotic depression is described. The ECT-induced akathisia responded successfully to mianserin. It seems that the beneficial effect of low-dose mianserin (15 mg/day) is related to its prominent antagonistic activity at the 5-HT2A/5-HT2C receptors.

Verapamil treatment in clozapine-induced sleep-related enuresis: a case report.

Enuresis is an embarrassing rare side effect of clozapine treatment. Using single-blind placebo-control design, the antienuretic activity of the calcium channel blocker verapamil (up to 80 mg/day per os, at 21.00 hours) was evaluated in a schizophrenic patient with comorbid obsessive-compulsive disorder (OCD) who developed nocturnal functional enuresis during clozapine treatment. Verapamil (80 mg/day) displayed antienuretic activity. No correlation between the bradycardiac effect and the antienuretic activity of verapamil was detected.