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IN THIS ISSUE:
June 2007

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

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.

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

Mifepristone for Psychotic Depression?

June 2007

When major depression is accompanied by symptoms of psychosis, usual treatments are either electroconvulsive therapy (ECT) or combined antipsychotic and antidepressant medications.1 (Of note, Andreescu et al recently observed a low frequency of antipsychotic prescribing in the community for patients with psychotic depression.2) Patients with psychotic depression are known to have excessive activity in their hypothalamic-pituitary-adrenal axis, demonstrated by high levels of corticosteroid excretion and difficulty suppressing cortisol secretion with dexamethasone (Decadron and others). Mifepristone (Mifeprex), an abortifacient and antineoplastic agent, is a progesterone antagonist and, at higher doses, an antagonist of glucocorticoid receptors. Preliminary results suggested mifepristone might be an effective treatment for psychotic depression (BTP 2003;26:1),3,4 but recent findings are not as encouraging.

Simpson and coauthors studied 20 patients with a major depressive episode with psychotic features.5 Patients were given a 6-day, open-label course of mifepristone with no other psychotropic agents. Significant improvement from baseline was observed in depression and global ratings between weeks 1 and 4 but not for a second month of observation.

Flores and associates studied 30 patients with psychotic depression, who were treated for 8 days with either mifepristone or placebo in a random-assignment, double-blind fashion.6 Symptoms of psychosis improved significantly with mifepristone (compared with placebo) as measured by the Brief Psychiatric Rating Scale (BPRS). However, depression, measured by the Hamilton Depression Rating Scale, showed no difference between mifepristone and placebo.

In a separate and much larger trial, DeBattista et al studied 221 patients, again with psychotic major depression.7 In double-blind fashion, they were randomly assigned to receive 7 days of treatment with either mifepristone or placebo. Similar to the results of Flores et al, patients treated with mifepristone were significantly more likely than those treated with placebo to achieve response criterion on the BPRS. However, improvement of depression did not differ between active and placebo treatments.

Major depression with psychotic features is a serious condition, which usually renders patients unable to function and can be lethal. To replace the standard treatments of ECT or an antidepressant-antipsychotic combination, a new intervention has to effectively combat both depression and psychosis. Results from these double-blind studies with mifepristone are disappointing.

1American Psychiatric Association: Practice guideline for the treatment of patients with major depressive disorder. Am J Psychiatry 2000;157(Suppl 4):1-45.

2Andreescu C, Mulsant BH, Peasley-Miklus C, Rothschild AJ, Flint AJ, Heo M, Caswell M, Whyte EM, Meyers BS, STOP-PD Study Group: Persisting low use of antipsychotics in the treatment of major depressive disorder with psychotic features. J Clin Psychiatry 2007;68:194-200.

3Belanoff JK, Flores BH, Kalezhan M, Sund B, Schatzberg AF: Rapid reversal of psychotic major depression using mifepristone. J Clin Psychopharmacol 2001;21:516-521.

4Belanoff JK, Rothschild AJ, Cassidy F, DeBattista C, Baulieu EE, Schold C, Schatzberg AF: An open label trial of C-1073 (mifepristone) for psychotic major depression. Biol Psychiatry 2002;52:386-392.

5Simpson GM, El Sheshai A, Loza N, Kingsbury SJ, Fayek M, Rady A, Fawzy W: An 8-week open-label trial of a 6-day course of mifepristone for the treatment of psychotic depression. J Clin Psychiatry 2005;66:598-602.

6Flores BH, Kenna H, Keller J, Solvason HB, Schatzberg AF: Clinical and biological effects of mifepristone treatment for psychotic depression. Neuropsychopharmacology 2006;31:628-636.

7DeBattista C, Belanoff J, Glass S, Khan A, Horne RL, Blasey C, Carpenter LL, Alva G: Mifepristone versus placebo in the treatment of psychosis in patients with psychotic major depression. Biol Psychiatry 2006;60:1343-1349.