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.

Ziprasidone outcome and tolerability: a practical clinical trial with plasma drug levels.

INTRODUCTION: The aim of this study was to evaluate clinical outcomes and the tolerability of ziprasidone in relation to its plasma levels. METHODS: Thirteen inpatients affected by schizophrenia were included in the study after an acute exacerbation phase. Ziprasidone monotherapy was administered for a period of eight weeks at a mean dose of 123.07+/-30.38 mg/day. Plasma concentrations were measured by high-performance liquid chromatography. RESULTS: Nine patients completed the study. A significant clinical improvement was observed, especially in negative symptoms ( P<0.05), and there was a significant improvement in extrapyramidal symptoms ( P<0.01). Clinical laboratory tests, such as ECG and weight, did not significantly change from baseline. Plasma ziprasidone levels ranged from 20 ng/mL to 160 ng/mL (mean: 75.8 ng/mL) and were significantly related to the improvement in negative symptoms. DISCUSSION: The study showed that ziprasidone was effective and tolerable, that use of ziprasidone was characterized by an absence of extrapyramidal symptoms and weight gain, and that no alterations in clinical laboratory tests occurred. The findings suggest a relationship between plasma levels and the clinical response to negative symptoms of schizophrenia.

Substance abuse in first-episode schizophrenic patients: a retrospective study.

Several studies suggest a high comorbidity of substance abuse and schizophrenia, associated with higher frequency of relapse, more positive symptoms and depression, cognitive impairment, poorer outcome and treatment response. A high incidence of substance abuse is also observed in first-episode patients. Among patients with substance abuse, the onset precedes the onset of psychosis of several years in most cases. All the patients with a first episode of schizophrenia, at first admission to the Psychiatric Service of Diagnosis and Treatment of Ospedale Maggiore of Milan during the years 1990 to 2004, have been included in our study.The clinical evaluation has been obtained considering the following items of Brief Psychiatric Rating Scale (BPRS): conceptual disorganization, depressed mood, hostility, hallucinations, unusual content of thought.The results showed that 34.7% of first-episode schizophrenic patients had a lifetime history of substance abuse. The age of onset of schizophrenia is significantly lower for drug abusers than for patients without any type of abuse and for alcohol abusers (p < 0.005). In multi drug abusers, cannabis resulted the most frequently used (49%), followed by alcohol (13%), and cocaine (4%). Substance abusers have obtained a significant higher score in "thought disturbance" item (p < 0.005) and in "hostility" item (p < 0.005) compared to non substance abusers. Non drug abusers showed lower mean scores of "hostility" item compared to cocaine abusers and multi drug abusers (p < 0.005). Our findings seem to indicate that substance abuse in the early course of illness determines an earlier onset of schizophrenia and increases severity of some psychotic symptoms like "hallucination" and "unusual content of thought". Therefore persons incurring a risk of schizophrenia may be warned of the possible relation between substances and psychosis and have to be counselled against the use of them.

Efficacy of clozapine in a non-schizophrenic patient with psychogenic polydipsia and central pontine myelinolysis.

Clozapine is an atypical antipsychotic drug that has been demonstrated to be a highly effective treatment for polydipsia in schizophrenic patients. The authors report the first case of a non-schizophrenic patient affected by polydipsia and central pontine myelinolysis who was successfully treated with clozapine.

Predictive value of amino acids in the treatment of major depression with fluvoxamine.

Sixteen outpatients (mean age +/- SD 50.18 +/- 11.55 years; 11 females and 5 males) affected by major depression without melancholia (DSM-IV) were included in the study. The control group consisted of 11 healthy volunteers (mean age +/- SD 39.90 +/- 13.39 years; 2 females and 9 males). Patients were treated with fluvoxamine (FVX) 100-300 mg daily. Clinical assessment was performed using the Hamilton Rating Scales for Anxiety and Depression (HRS-A; HRS-D) and the Clinical Global Impression Scale (CGI) at basal time (T(0)), after 4 weeks and after 8 weeks (T(8)). Plasma and platelet amino acid levels were determined at T(0) in all the subjects and also at T(8) in depressed patients. A significant clinical improvement was observed in depressed patients according to the HRS-A (p = 0.004), HRS-D (p = 0.008) and CGI (p = 0.002). A negative correlation (r = -0.53, p = 0.049) was found between platelet levels of valine and HRS-D improvement rate. Patients showed significantly higher tyrosine/large neutral amino acids (LNAAs) and lower tryptophan/LNAAs, ratios which could represent an index of good response to a serotonergic drug like FVX.

"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.

Lithium safety in the prophylaxis of bipolar disorders: a study with plasma levels.

From many decades efficacy of lithium salts, as mood stabilizers, has been largely recognized, but their tolerability, in particular during intermediate or long-term treatments is still discussed. The most frequently described side effects can affect several organs. Aim of the study was to evaluate lithium carbonate tolerability after a "brief" (1 month-4 years), "intermediate" (5-9 years) and "longterm" (10-21 years) treatment of patients affected by Bipolar Disorders (BD). 27 patients (14 males, 13 females), aged from 20 to 78 years (mean 49.03 years +/- 14.61 SD), affected by BD, type I, according to DSM IV criteria were included into the study. Our data suggest a good tolerability of lithium salts without significant differences among the three different periods of treatment.