Flupenthixol is an antipsychotic drug with known mood-elevating properties. Its propensity to induce manic symptoms has not been investigated.

We describe six patients, four with schizophrenia and two with bipolar disorder, in whom flupenthixol treatment was associated with emergence of manic symptoms.

Patients treated with flupenthixol should be carefully monitored for the emergence of manic symptoms.

To assess changes in body mass and metabolic profiles in patients with first-episode schizophrenia receiving standardised, assured treatment and to identify predictors and moderators of the effects.

We investigated the changes in body mass, fasting blood glucose and lipids in 107 largely antipsychotic naïve, first-episode schizophrenia patients who were treated according to a standard algorithm with long-acting injectable flupenthixol decanoate over 12 months.

Eighty-three (78%) participants completed the 12 months of treatment, and 104 (97%) received 100% of the prescribed injections during their participation. There were significant increases in BMI (P < .0001), waist circumference (P = 0.0006) and triglycerides (P = 0.03) and decrease in HDL (P = 0.005), while systolic (P = 0.7) and diastolic blood pressure (P = 0.8), LDL (P = 0.1), cholesterol (P = 0.3), and glucose (P = 0.9) values did not change over time. The triglyceride: HDL ratio increased by 91%. Change in BMI was only correlated with change in triglycerides (P = .008). The only significant predictor of BMI increase was non-substance abuse (P = .002).

The risks of weight gain and metabolic syndrome associated with antipsychotic treatment in first-episode schizophrenia are not restricted to second generation antipsychotics. This is a global problem, and developing communities may be particularly susceptible.

Progressive brain volume reductions have been described in schizophrenia, and an association with antipsychotic exposure has been reported.

We compared percentage changes in grey and white matter volume from baseline to month 12 in 23 previously antipsychotic-naïve patients with a first episode of schizophrenia or schizophreniform disorder who were treated with the lowest effective dose of flupenthixol decanoate depot formulation, with 53 matched healthy individuals. Total antipsychotic dose was precisely calculated and its relationship with brain volume changes investigated. Relationships between volumetric changes and treatment were further investigated in terms of treatment response (changes in psychopathology and functionality) and treatment-related adverse-events (extrapyramidal symptoms and weight gain).

Excessive cortical volume reductions were observed in patients [−4.6 (6.6)%] v. controls [−1.12 (4.0)%] (p = 0.009), with no significant group differences for changes in subcortical grey matter and white matter volumes. In a multiple regression model, the only significant predictor of cortical volume change was total antipsychotic dose received (p = 0.04). Cortical volume change was not significantly associated with the changes in psychopathology, functionality, extrapyramidal symptoms and body mass index or age, gender and duration of untreated psychosis.

Brain volume reductions associated with antipsychotic treatment are not restricted to poor outcome patients and occur even with the lowest effective dose of antipsychotic. The lack of an association with poor treatment response or treatment-related adverse effects counts against cortical volume reductions reflecting neurotoxicity, at least in the short term. On the other hand, the volume reductions were not linked to the therapeutic benefits of antipsychotics.