Psychotic depression: State-of-the-art algorithm improves odds for remission
Consider an antipsychotic, even when paranoia or cognitive changes are more obvious than delusions or hallucinations.
To our knowledge, no data indicate how long to continue lithium augmentation. We start older adults on 300 mg/d and younger adults on 600 mg/d and increase by 300 mg per week. Target serum levels are 0.5 to 0.8 mEq/L, and maximum dosage is 1,200 mg/d for young adults and 900 mg/d for frail or elderly patients. We follow thyroid, renal, and hydration status and monitor for weight gain, tremors, cognitive slowing, and GI disturbances.
Other second-line options. Sufficient data support using the second-line drugs in our algorithm as first-line agents. However, the second-line agents pose a greater risk of adverse effects and decreased tolerability than SSRIs plus atypical antipsychotics. Second-line options include:
- SSRIs plus conventional antipsychotics
- amoxapine, a derivative of the conventional antipsychotic loxapine
- venlafaxine or TCAs plus atypical antipsychotics.
As with first-line therapy, 8 to 12 weeks is an adequate trial for second-line medications. ECT may be considered for patients who fail to respond to medications or experience complications.
SSRI/conventional antipsychotic. Our group used fluoxetine, 20 to 40 mg/d, plus perphenazine, 32 mg/d, in the first study of combined SSRI/conventional antipsychotic therapy for patients with psychotic depression.20 After 5 weeks, 22 of 30 patients’ HRSD and BPRS scores were reduced by >50%.
Amoxapine monotherapy. Anton and Burch21 compared amoxapine, 400 mg/d, with amitriptyline, 200 mg/d, plus perphenazine, 32 mg/d. Response rates (>50% reduction on the HRSD) were 71% and 81% for the two groups, respectively. Extrapyramidal symptoms (EPS) were more frequent with the combination therapy.
Venlafaxine’s mechanism of action is thought to be similar to that of TCAs, and we know from the Spiker study15 that TCAs are effective in treating psychotic depression. To our knowledge, venlafaxine dosages for psychotic depression have not been studied; 75 to 375 mg/d is recommended for nonpsychotic depression. Potential side effects include insomnia, nervousness, nausea, headache, dry mouth, fatigue, and elevations of supine diastolic blood pressure.
Third-line therapy. Clozapine may be considered when second-line options do not achieve adequate results.22 When making this choice, consider the need for biweekly blood monitoring and the risk of serious side effects such as agranulocytosis and seizures.
Maintenance therapy
Psychotic depression has a higher relapse rate than nonpsychotic depression. Relapse rates are 50 to 92% in patients with psychotic depression, and recurrence often develops within 2 to 14 months after recovery from the index episode.23 With little data on which to base a maintenance regimen, we recommend that you continue antipsychotics for 4 months after the acute episode resolves.
Recently our group reported that after a taper of perphenazine—following 4 months of treatment with fluoxetine and perphenazine—22 of 30 patients (73%) showed no signs of relapse over the next 11 months.24 We usually maintain patients on antidepressants indefinitely.
Related resources
- DeBattista C, Rothschild AJ, Schatzberg AF. A dynamic algorithm for the treatment of psychotic major depression. Psychiatric Ann 2002;32:681-91.
- Rothschild AJ. Challenges in the treatment of depression with psychotic features. Biol Psychiatry 2003;53:680-90.
- National Institutes of Health. https://www.clinicaltrials.gov. Enter “Medication treatment for psychotic depression” in “Search clinical trials” field, then click on appropriate link.
Drug brand names
- Amitriptyline • Elavil
- Amoxapine • Asendin
- Bupropion • Wellbutrin
- Chlorpromazine • Thorazine
- Clozapine • Clozaril
- Desipramine • Norpramin
- Fluoxetine • Prozac
- Imipramine • Tofranil
- Loxapine • Loxitane
- Olanzapine • Zyprexa
- Paroxetine • Paxil
- Perphenazine • Trilafon
- Risperidone • Risperdal
- Quetiapine • Seroquel
- Venlafaxine • Effexor
Disclosure
Dr. Bell reports no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.
Dr. Rothschild receives research support from Bristol-Myers Squibb, Eli Lilly and Co., Merck & Co., Wyeth Pharmaceuticals, and the National Institute of Mental Health. He is a consultant to and/or speaker for Forest Pharmaceuticals, Eli Lilly and Co., Abbott Laboratories, Bristol-Myers Squibb, and Pfizer Inc. In the past, he has been a consultant to and received research grants from Corcept Therapeutics.
