Clinical outcome and tolerability of duloxetine in the treatment of major depressive disorder: a 12-week study with plasma levels.

Duloxetine (DLX) is a dual serotonin and norepinephrine reuptake inhibitor that has been recently approved for the treatment of major depressive disorder (MDD). However, little is known about the relationship between DLX plasma levels and clinical response. The aims of this open-label study were 1) to assess clinical outcome and tolerability of DLX by means of clinician and patient assessments and 2) to evaluate the value of plasma DLX levels as predictors of clinical response and tolerability. This was a naturalistic, open-label study of 45 outpatients affected with MDD (16 men and 29 women), who received DLX at doses of 30-120 mg/day and were evaluated at baseline (T0) and after 2, 4 and 12 weeks (T1-3). The assessments included the Hamilton Rating Scales for Depression (HRSD) and Anxiety (HRSA), Clinical Global Impression-Severity (CGI-S), Beck's Depression Inventory (BDI) and a mood visual analogue scale (VAS). Compared with T0, there were significant improvements in HRSD at T1, T2 and T3 (P < 0.001), in HRSA, CGI-S and the self-administered BDI at T2 and T3 (P < 0.001), and in the VAS scores shown at T3 (P = 0.01). DLX treatment was safe and well tolerated. Plasma DLX levels at T2 ranged from 5 to 135 ng/mL (mean +/- SD = 53.56 +/- 39.45) and correlated almost significantly with the DLX dose (r = 0.35; P = 0.069). There was a significant curvilinear quadratic relationship between the improvement of HRSA scores and plasma DLX levels (R(2) = 0.27; P = 0.02). The incidence of anxiety or irritability was associated with the highest plasma levels. Our findings suggest that monitoring plasma DLX levels may be helpful in predicting better treatment responses and tolerability. The present data seem to suggest an optimal anxiolytic efficacy of DLX at intermediate plasma levels.

Clinical outcome and olanzapine plasma levels in acute schizophrenia.

PURPOSE: This open label study was performed to evaluate the relationship between the plasma concentration of olanzapine and the response in acute schizophrenic inpatients. MATERIAL AND METHODS: A total of 54 inpatients, 38 males and 16 females, age ranging from 18 to 75 years, affected by Schizophrenia (DSM IV criteria) during an exacerbation phase were included in the study. Olanzapine (OLZ) was started at a dose of 5-20 mg/day and was increased to a mean dose of 15.27 mg +/-5.53 S.D. Patients were evaluated at baseline, and after 2 weeks, by using BPRS, PANNS, HRS-D, EPSE, and ACS. RESULTS: BPRS and total PANSS showed a statistically significant improvement at the end of the study. Olanzapine plasma levels (PL) ranged from 5 to 120 ng/ml (mean 33.15 ng/ml +/- 28.28 S.D.) and showed a positive correlation with OLZ dosage. A significant curvilinear correlation between OLZ PL and clinical improvement (BPRS, PANSS and HRS-D percent of amelioration) was observed. CONCLUSION: Olanzapine plasma level determination seems to be a useful tool in optimizing acute treatment particularly for more problematic cases.

Gabapentin and the Prophylaxis of Bipolar Disorders in Patients Intolerant to Lithium.

OBJECTIVE: Gabapentin (GBP) is a new anticonvulsant drug that has shown efficacy in the treatment of epilepsy, several neurological disorders (pain syndromes, acquired nystagmus, Huntington's chorea, amyotrophic lateral sclerosis), and more recently in the treatment of bipolar disorders. The aim of this preliminary study was to assess the efficacy of GBP as a mood stabiliser in bipolar disorders. The adverse events of GBP were also evaluated. PATIENTS AND METHODS: 21 outpatients, 13 females and 8 males (mean age ± SD: 51.90 ± 11.51 years) affected by bipolar disorder (BD), in partial remission (DSM IV) and intolerant to lithium, were treated with GBP at a dose ranging from 300 to 2400 mg/day (mean ± SD: 1010.86 ± 268.55mg; 13.81 ± 4.21 mg/kg) for 1 year. Clinical assessments were performed with the Brief Psychiatric Rating Scale (BPRS), the Hamilton Rating Scale for Depression (HRS-D), the Hamilton Rating Scale for Anxiety (HRS-A) and the Manic Rating Scale (MRS) at baseline (T0), after 15 days (T0.5), after 30 days (T1), and then every month for 12 months. RESULTS: Mean HRS-D, HRS-A and MRS scores did not show any significant variation during the study. Only one patient showed a clinical relapse. The most frequent adverse events reported by patients were dizziness (1%), dry mouth (1%) and sedation (0.5%). There was a significant negative correlation between GBP dosage (mg/kg) and HRS-A score. Mean leucocyte and neutrophil counts showed a significant increase during the study. CONCLUSIONS: These preliminary data show potential efficacy and good tolerability of GBP in the prophylaxis of BD, but double-blind studies are required.

"Postpsychotic depression" and residual schizophrenia in a mental health hospital.

Forty three patients, mean age 55.20 +/- 9.27 SD, affected by Schizophrenia Residual Type (DSM IV, RDC criteria) and treated with neuroleptic drugs for a mean of 25.42 years (+/- 4.12 SD) were included into the study. Clinical evaluation was cross-sectional assessed by BPRScale, SAPS, SANS, HRS-D, EPSE. ACS and MMSE. Seventy percent of patients presented a "postpsychotic depression" (42%, mild; 16%, moderate and 12% serious). "Postpsychotic depression" does not seem to be influenced by neuroleptics, but it seems to be a component of residual schizophrenia in patients with a long lasting permanence in a mental hospital.