June 2007

rTMS: Inferior to ECT?
Repetitive transcranial magnetic stimulation (rTMS) is not as efficacious as electroconvulsive therapy (ECT) in patients referred for ECT.

Psychotropics and Fracture Risk
Patients (especially elderly ones) taking psychiatric medications are at increased risk for fractures.

Riluzole Augmentation for Depression
Preliminary evidence suggests riluzole (Rilutek) may be helpful in treating mood and anxiety disorders.

CBT Beats Zopiclone for Insomnia in Elderly
Cognitive behavioral therapy (CBT) was superior to zopiclone (Ambien) for chronic primary insomnia.

Alternative Medicines Are Commonly Used
Surveys show alternative medicines used by more than half of US population.

Hyponatremia with Antidepressants
Hyponatremia reported in patients treated with escitalopram (Lexapro) or duloxetine (Cymbalta).

In Brief
Dosing Strategies for Risperidone Long-Acting Injection; Deaths Associated with Methadone Treatment for Pain

Prolactin Levels and Associated Side Effects with Risperidone
Initial elevation of prolactin levels with risperidone (Risperdal) returns to normal with long-term treatment.

Mifepristone for Psychotic Depression?
Treatment with mifepristone (Mifeprex) improves psychosis but not depression in patients with psychotic depression.

An NSAID for Schizophrenia?
Adjunctive celecoxib (Celebrex) may be beneficial for treating schizophrenia.

Riluzole Augmentation for Depression

June 2007

Most antidepressants inhibit synaptic reuptake of monoamine neurotransmitters. A growing body of research suggests that the glutamatergic system also may be involved in the pathophysiology of mood disorders and, therefore, drugs that reduce glutamatergic tone could play a role in treating depression.

Riluzole (Rilutek) is labeled for the treatment of amyotrophic lateral sclerosis (ALS). In experimental animals, it inhibits excitotoxic injury, presumably by decreasing glutamate release and increasing its uptake. Open-label trials have suggested a possible role for riluzole by itself as a treatment for depression and anxiety and as a possible adjunct to lithium for treating bipolar depression. Last year, we described a study in which adjunctive riluzole benefited patients with treatment-resistant obsessive compulsive disorder (BTP 2006;29:28).1 In a recent trial, Sanacora and coworkers used riluzole to augment antidepressant medication in 13 patients who had residual depression symptoms.2

The subjects were seven women and six men, aged 35 to 62 years. All were suffering from an episode of major depression, and many had a chronic condition. At the time they entered this trial, patients were receiving a wide range of antidepressants and other psychotropic agents.

In open-label fashion, the investigators added 50 mg of riluzole bid to the ongoing treatment regimen. After 6 weeks of treatment, the mean depression score on the Hamilton Depression Rating Scale decreased by an average of 36% (P < .005). Anxiety symptoms also fell. These apparent effects of riluzole were significant at the end of the first week of treatment and persisted for the 12-week duration of the study. The most frequent adverse effect with riluzole was fatigue, for which investigators lowered doses for two subjects. One patient experienced visual hallucinations.

As of now, riluzole can be viewed as an interesting "lead" for the treatment of mood and anxiety disorders. However, data are preliminary, and definitive answers will require rigorous trials with much larger samples.

1Coric V, Taskiran S, Pittenger C, Wasylink S, Mathalon DH, Valentine G, Saksa J, Wu YT, Gueorguieva R, Sanacora G, Malison RT, Krystal JH: Riluzole augmentation in treatment-resistant obsessive-compulsive disorder: An open-label trial. Biol Psychiatry 2005;58:424-428.

2Sanacora G, Kendell SF, Levin Y, Simen AA, Fenton LR, Coric V, Krystal JH: Preliminary evidence of riluzole efficacy in antidepressant-treated patients with residual depressive symptoms. Biol Psychiatry 2007;61:822-825.