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.

Background and Aims:Duloxetine (DLX) is approved for treatment of Major Depressive Disorder (MDD).Aims of this study were to assess the clinical outcome of DLX in the treatment of MDD, with efficacy measures based on clinician and patient assessment, and to evaluate the predicitve value of DLX plasma levels on clinical response.Methods:45 out-patients affected by MDD were included in the study and prescribed 30-120 mg/day of DLX for 12 weeks.Patients were evaluated at T0, after 2 (T1), 4 (T2), and 12 weeks (T3), by using HAMD21, HAMA, CGI-S, and the self-rating scales BDI and VAS. Plasma samples were collected at T2.Results:Responders (50% reduction in HAMD21) were 60% and remitters (HAMD21 ≤7) were 56%. HAMD21 showed a significant improvement at T1, T2, T3 vs T0. HAMA and CGI-S showed a significant improvement at T2, T3 vs T0.15 (33%) patients discontinued the treatment.Blood pressure, heart rate, and body weight did not show relevant changes.DLX plasma levels ranged from 5 ng/ml to 135 ng/ml (mean 53.56 ± 39.45 SD). The incidence of side effects irritability and anxiety was found to be significantly correlated with the highest DLX level/dose (mean 1.6 ng/ml/mg ± 0.29 SD) (p=0.02).We observed a curvilinear relationship between HAMD21 percentage of amelioration at T2 and DLX plasma levels/dose (mg/kg) (y=22.74+0.78x-0.0038x2, R2=0.134; p=0.23).Conclusion:Good medium-term clinical response, but plasma levels showed an increased of adverse events at higher values, reducing the advantages of dose escalation.

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.