Corticosteroid psychosis: Stop therapy or add psychotropics?
Off-label antipsychotics, mood stabilizers, and anticonvulsants could help
Corticosteroid-induced psychosis: Adjunctive treatment studies
| Medication and source | Patient population | Results |
|---|---|---|
| Olanzapine (Brown et al, 20058) | 12 outpatients experiencing manic or mixed symptoms received olanzapine, mean 8.5 mg/d | Reductions on YMRS, HRSD, and BPRS with no change in extrapyramidal symptom side-effect scales, weight, or glucose measurements |
| Lithium (Falk et al, 19799) | 27 patients diagnosed with multiple sclerosis or retrobulbar neuritis treated with corticotropin received lithium | 38% of lithium patients developed psychiatric symptoms compared with 62% of controls |
| Phenytoin (Brown et al, 200510) | 39 patients received phenytoin, 300 mg/d, or placebo at prednisone therapy initiation | Patients receiving phenytoin reported a smaller increase in ACT score compared with controls |
| Levetiracetam (Brown et al, 200711) | 30 outpatients receiving corticosteroids randomized to levetiracetam, 1500 mg/d, or placebo | No significant change in HRSD, YMRS, or ACT scores |
| Lamotrigine (Brown et al, 200312) | 5 patients on chronic corticosteroid treatment received open-label lamotrigine, mean dose 340 mg/d | No significant difference in HRSD, YMRS, or the depression subscale of the Internal State Scale |
| ACT: Internal State Scale Activation subscale; BPRS: Brief Psychiatric Rating Scale; HRSD: Hamilton Rating Scale for Depression; YMRS: Young Mania Rating Scale | ||
Antipsychotics
Open-label trial. Olanzapine reduced psychiatric symptoms in a 5-week, open-label trial of 12 outpatients experiencing manic or mixed symptoms secondary to corticosteroids.8 At baseline, patients had a mean score of 15.25 on the Young Mania Rating Scale (YMRS) on a mean prednisone dose of 14.4 mg/d. After receiving olanzapine, 2.5 mg/d titrated to a maximum 20 mg/d (mean 8.5 mg/d), subjects demonstrated a significant decrease on the YMRS (P=.002), Hamilton Rating Scale for Depression (HRSD) (P=.005), and Brief Psychiatric Rating Scale (BPRS) (P=.006) with no change in extrapyramidal side-effect scales, weight, or glucose measurements.
Case reports. Among antipsychotics, olanzapine has the greatest number of case reports for treating corticosteroid-induced psychosis, mainly for mania.13-15 Benefit with olanzapine was demonstrated at dosages from 2.5 to 15 mg/d and improvement occurred within days to weeks. Several patients remained symptom-free with olanzapine and continued corticosteroid therapy.
Other reports describe benefit with risperidone for a variety of psychiatric symptoms—including hypomania, hallucinations, and delusions—associated with corticosteroid therapy.16-19 Risperidone dosing ranged from 1 to 4 mg/d, and symptoms improved within days to weeks.
One case report describes quetiapine for the treatment of corticosteroid-induced mania.20 The patient’s symptoms improved within 10 hours of initiating quetiapine, 25 mg/d, and YMRS score decreased from 31 before therapy to 5 at discharge. No case reports exist for ziprasidone or aripiprazole.
Mood stabilizers
Cohort study. One study suggests that lithium may be effective for preventing and treating corticosteroid-induced psychosis. A retrospective cohort study examined records of patients diagnosed with multiple sclerosis or retrobulbar neuritis who were treated with corticotropin.9 Corticotropin has been reported to cause psychotic reactions in up to 11% of patients through a mechanism thought to mirror corticosteroid-induced psychosis (Box).21-23 Psychiatric symptoms developed in 38% of patients treated with lithium compared with 62% of controls. No patients pretreated with lithium maintained at 0.8 to 1.2 mEq/L reported mood disturbances or psychotic reactions.
Case reports. Among mood stabilizers, lithium has the greatest number of case reports on its use for prevention and treatment of corticosteroid-induced psychosis. In these reports, patients pretreated with lithium did not experience a relapse of psychosis related to chronic corticosteroid therapy.24-27 Case reports also describe benefit with valproic acid and carbamazepine.28-30
Anticonvulsants
Trials. In a 1-week trial, 39 patients without previous psychiatric diagnosis or psychotropic use were randomly assigned to phenytoin, 300 mg/d, or placebo as prednisone therapy was initiated.10 Compared with placebo, the phenytoin group reported a smaller increase on the Internal State Scale Activation subscale (ACT), a self-report measure of mania symptom severity. No significant differences were found on the YMRS or HRSD scales. Based on the ACT scale finding, the authors concluded that phenytoin attenuated manic or hypomanic effects of prednisone.
A study of levetiracetam, 1500 mg/d, showed no significant change in HRSD, YMRS, or ACT scores from baseline to end point for either levetiracetam or placebo.11
A 12-week, open-label trial of lamotrigine in 5 patients receiving corticosteroids continuously for 6 months showed no significant difference in mood changes as measured by the HRSD, YMRS, or the depression sub-scale of the Internal State Scale.12
Case reports show that lamotrigine and gabapentin have been used effectively to prevent manic symptoms in patients receiving corticosteroid therapy.31,32
Treatment recommendations
Establishing a treatment algorithm for corticosteroid-induced psychosis is hampered by the lack of prospective placebo-controlled trials. However, most case reports describe benefit from administrating atypical antipsychotics and lithium.
