November 2010

SAMe for Depression?
The first placebo-controlled trial of SAMe as an adjunct to antidepressants in patients with treatment-resistant depression has yielded positive results.

IV Ketamine for Bipolar Depression
In a randomized, add-on trial, one infusion of IV ketamine improved depressive symptoms in patients with treatment-resistant bipolar depression.

Receptor-Binding Profiles of New Antipsychotics
The new antipsychotics paliperidone (Invega), iloperidone (Fanapt), and asenapine (Saphris) have different receptor-binding properties.

Sex Steroids for Schizophrenia?
In a double-blind trial, low-dose pregnenolone but not dehydroepiandrosterone (DHEA) improved outcomes in patients with schizophrenia when used to augment antipsychotic treatment.

In Brief
FDA Advisory Committee Votes Against Approval of Weight-Loss Drug Lorcaserin; Neonatal Levels of Vitamin D Associated with Increased Schizophrenia Risk; Warning Issued that Anticonvulsant Drug Lamotrigine (Lamictal) Can Cause Aseptic Meningitis

ADHD Symptoms, Food Additives, and Genetic Variations
Genetic variations may underlie differences in how artificial food dyes affect attention-deficit/hyperactivity disorder (ADHD) symptoms in children.

Sex Steroids for Schizophrenia?

November 2010

As we note frequently in these pages, treatments for people with schizophrenia are far from optimal (BTP 2009;32:21-22). And even with the best possible treatment, many patients are left with substantial residual symptoms. Scientists and clinicians are constantly seeking new avenues to benefit this population. One such route may involve neurosteroids.

Reported to have a modulatory effect on neuronal excitability and synaptic plasticity, the neurosteroids pregnenolone and dehydroepiandrosterone (DHEA) are associated with mood regulation and response to stress. They also appear to improve cognitive performance and may be involved in the pathophysiology of several psychiatric disorders, including schizophrenia. Patients with schizophrenia have been observed to have low circulating pregnenolone levels, and clozapine (Clozaril and others) and olanzapine (Zyprexa) elevate brain pregnenolone levels in rats.

Ritsner and colleagues studied pregnenolone and DHEA as adjunctive treatment to antipsychotic drug therapy in patients with schizophrenia.1 Pregnenolone had not previously been studied in this capacity and trials of DHEA had produced conflicting results.

In a double-blind, two-center, self-funded trial, the authors randomly assigned 58 patients with chronic schizophrenia or schizoaffective disorder to continue taking their antipsychotics plus adjunctive treatment with one of the following: 30 or 200 mg daily of pregnenolone, 400 mg daily of DHEA, or placebo for 8 weeks. Participants—13 women and 45 men, aged 23 to 55 years—were taking a wide range of first- and second-generation antipsychotics.

Patients who received the lower pregnenolone dose (30 mg/day) had significantly greater reductions in positive symptom scores and extrapyramidal side effects and improvement in attention and working memory compared with patients taking placebo. By contrast, neither the higher dose of pregnenolone (200 mg/day) nor DHEA improved outcomes. Negative symptoms and akathisia were not benefited by any of the treatments. Both pregnenolone and DHEA were well tolerated.

The authors caution that their sample was relatively small and the study duration comparatively short. Nonetheless, their observation of a benefit from low-dose pregnenolone as an augmentation to antipsychotic treatment is grounds for guarded optimism. This creative approach merits further study.

1Ritsner MS, Gibel A, Shleifer T, Boguslavsky I, Zayed A, Maayan R, Weizman A, Lerner V: Pregnenolone and dehydroepiandrosterone as an adjunctive treatment in schizophrenia and schizoaffective disorder: An 8-week, double-blind, randomized, controlled, 2-center, parallel-group trial. J Clin Psychiatry, in press.