Patients with a history of suboptimal response to conventional treatments may show cognitive benefits from newer antipsychotic drugs, and there may be differences between atypical antipsychotic drugs in their patterns of cognitive effects.

Objective To study the association between prescribed antipsychotic drugs and outcome in schizophrenia or schizoaffective disorder in the community. Design Prospective cohort study using national central registers. Setting Community care in Finland. Participants Nationwide cohort of 2230 consecutive adults hospitalised in Finland for the first time because of schizophrenia or schizoaffective disorder, January 1995 to December 2001. Main outcome measures Rates of discontinuation of drugs (all causes), rates of rehospitalisation, and mortality associated with monotherapy with the 10 most commonly used antipsychotic drugs. Multivariate models and propensity score methods were used to adjust estimates of effectiveness. Results Initial use of clozapine (adjusted relative risk 0.17, 95% confidence interval 0.10 to 0.29), perphenazine depot (0.24, 0.13 to 0.47), and olanzapine (0.35, 0.18 to 0.71) were associated with the lowest rates of discontinuation for any reason when compared with oral haloperidol. During an average follow-up of 3.6 years, 4640 cases of rehospitalisation were recorded. Current use of perphenazine depot (0.32, 0.22 to 0.49), olanzapine (0.54, 0.41 to 0.71), and clozapine (0.64, 0.48 to 0.85) were associated with the lowest risk of rehospitalisation. Use of haloperidol was associated with a poor outcome among women. Mortality was markedly raised in patients not taking antipsychotics (12.3, 6.0 to 24.1) and the risk of suicide was high (37.4, 5.1 to 276). Conclusions The effectiveness of first and second generation antipsychotics varies greatly in the community. Patients treated with perphenazine depot, clozapine, or olanzapine have a substantially lower risk of rehospitalisation or discontinuation (for any reason) of their initial treatment than do patients treated with haloperidol. Excess mortality is seen mostly in patients not using antipsychotic drugs.

In this prospective randomized trial, clozapine, olanzapine, and haloperidol were associated with an increase of plasma glucose level, and clozapine and olanzapine were associated with an increase in cholesterol levels. The mean changes in glucose and cholesterol levels remained within clinically normal ranges, but approximately 14% of the patients developed abnormally high glucose levels during the course of their participation in the study.

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These results, in contrast to a recently published report, show that the NESARC data are consistent with the consensus view on mental disorder and violence: there is a statistically significant, yet modest relationship between SMI (within 12 months) and violence, and a stronger relationship between SMI with substance use disorder and violence. These results also highlight the importance of premorbid conditions, and other contemporaneous clinical factors, in violent behavior.

The disposition of naltrexone during acute and chronic administration of 100-mg oral dose was studied in 4 subjects. Following an acute dose the mean (X) peak naltrexone plasma level was 43.6 +/- 29.9 ng/ml at 1 hr and for the major biotransformation product, beta-naltrexol, was 87.2 +/- 25.0 ng/ml at 2 hr. Twenty-four hours after the dose the X levels of naltrexone and beta-naltrexol declined to 2.1 +/- 0.47 and 17.6 +/- 5.0 ng/ml, respectively. Following chronic administration and X peak plasma levels of naltrexone and beta-naltrexol rose to 46.4 +/- 18.5 and 158.4 +/- 89.9 ng/ml at 1 hr, but by 24 hr both compounds declined to levels of the same order as in the acute state at 24 hr. Plasma levels of naltrexone and beta-naltrexol measured 24 hr after the daily doses of naltrexone throughout the study indicated that steady-state equilibrium was rapidly attained and that there was no accumulation of naltrexone and beta naltrexol in the plasma after chronic treatment on 100 mg oral doses. Biexponential kinetics were observed for naltrexone and beta-naltrexol in the first 24 hr. The half-life of naltrexone and beta-naltrexol decreased slightly from the acute to thechronic study from 10.3 +/- 3.3 to 9.7 +/- 1.1 hr and from 12.7 +/- 2.6 to 11.4 +/- 2.0 hr. The plasma levels of naltrexone declined slowly from 24 through 72 hr from 2.4 to 1.7 ng/ml, with an apparent half-life of 96 hr. The renal clearance data indicate that naltrexone is partially reabsorbed while beta naltrexol is actively secreted by the kidney. During acute and chronic naltrexone administration the mean fecal excretion was 2.1% and 3.6% while urinary excretion was 38% and 70% of the dose in a 24-hr period. Opiate antagonism to 25 mg heroin challenges was nearly complete through 48 hr after naltrexone. At 72 hr the objective responses reappeared to a greater extent than the subjective ones. Correlation coefficient (r) between naltrexone plasma levels and opiate antagonism was 0.91 and between individual half-life of naltrexone and opiate antagonism it was 0.99.

A common 44-base pair insertion/deletion polymorphism in the promoter region of the human serotonin transporter (5-HTT) gene has been observed to be associated with affective illness and anxiety-related traits. This biallelic functional polymorphism, designated long (L) and short (S), affects 5-HTT gene expression since the S promoter is less active than the L promoter. Since there is strong evidence of a disturbance in brain serotonergic transmission among antisocial, impulsive, and violent type 2 alcoholic subjects, we decided to test the hypothesis that the frequency of the S allele, which is associated with reduced 5-HTT gene expression, is higher among habitually violent type 2 alcoholics when compared with race and gender-matched healthy controls and non-violent late-onset (type 1) alcoholics. The 5-HTT promoter genotype was determined by a PCRbased method in 114 late onset (type 1) non-violent alcoholics, 51 impulsive violent recidivistic offenders with early onset alcoholism (type 2), and 54 healthy controls. All index subjects and controls were white Caucasian males of Finnish origin. The S allele frequency was higher among type 2 alcoholics compared with type 1 alcoholics ( 2 = 4.86, P = 0.028) and healthy controls ( 2 = 8.24, P = 0.004). The odds ratio for SS genotype vs LL genotype was 3.90, 95% Cl 1.37-11.11, P = 0.011 when type 2 alcoholics were compared with healthy controls. The results suggest that the 5-HTT 'S' promoter polymorphism is associated with an increased risk for early onset alcoholism associated with antisocial personality disorder and impulsive, habitually violent behavior.

Newer antipsychotics did not reduce violence more than perphenazine. Effective antipsychotics are needed, but may not reduce violence unrelated to acute psychopathology.