Olanzapine for treatment-resistant anxiety
Ms. A, age 62, was a retired high school teacher. Her primary care physician referred her to me for persistent, disabling anxiety. Her condition was recently worsened by a trial of escitalopram, 5 mg/d, which led her to visit the emergency department (ED). There she was prescribed lorazepam, 0.5 mg as needed, which helped her somewhat. Her medical conditions included prominent gastrointestinal (GI) symptoms, with nausea and a restricted diet; tinnitus; and chronic bilateral hand tremors. Her initial Patient Health Questionnaire-9 (PHQ-9) score was 11, and her Generalized Anxiety Disorder-7 (GAD-7) score was 10.
Initially, I encouraged Ms. A to exercise regularly, and I changed her lorazepam from 0.5 mg as-needed to 0.5 mg twice a day. I also referred her to a psychologist for psychotherapy. She showed limited improvement. I increased her lorazepam to 1 mg 3 times a day and started sertraline, 12.5 mg/d, but she soon experienced chest tightness and was admitted to the ED for observation and a cardiac workup. After she visited the ED, Ms. A stopped taking sertraline.
When I next saw Ms. A, she agreed to a trial of olanzapine, 2.5 mg/d at bedtime. Three weeks later, she told me, “I feel so much better.” Her scores on the PHQ-9 and GAD-7 were 0 and 1, respectively. Her GI complaints decreased, she had gained a little weight, and her tinnitus bothered her less. Lorazepam was gradually decreased and stopped.
After approximately 2 years, Ms. A had experienced no long-term adverse effects. We agreed to gradually discontinue olanzapine. Over the next 4 months, Ms. A decreased and stopped taking olanzapine at her own discretion.Three weeks after she stopped taking olanzapine, Ms. A reported that her psychiatric and GI symptoms had returned. She still maintained weekly visits with her psychotherapist. Her GI specialist asked if I could prescribe her olanzapine again. I restarted Ms. A on olanzapine, 2.5 mg/d at bedtime. By the next month, she said she felt much better (PHQ-9: 0; GAD-7: 1). I last saw Ms. A approximately 1 year ago.
Over the years, I have usually prescribed low-dose olanzapine alone or with other medications for patients with treatment-resistance who had no overt psychotic symptoms, I have used this medication for patients with “soft” psychotic thinking marked by severe anxiety, obsessions, compulsivity, perfectionism, and/or rumination.1 Evidence suggests olanzapine also may be effective for anorexia nervosa.2 There is good evidence for its use in the DSM-5 diagnosis of avoidant/restrictive food intake disorder (“a food avoidance emotional disorder”).3,4 In retrospect, Ms. A also likely met the criteria for the diagnosis of unspecified eating disorder. Despite extensive GI workup and follow-up, physical signs of GI pathology were equivocal.
Among antipsychotics, olanzapine most closely resembles clozapine, the only antipsychotic that has been proved more efficacious than others for psychotic symptoms.5 There is also some research suggesting that olanzapine may be more efficacious.6 Obsessions and perfectionism are associated with dopamine D4 receptor activity, and D1, D2, and D3 receptors are involved in normalizing cognition and reward.7 There are appropriate concerns about adverse effects, especially metabolic syndrome and obesity, with olanzapine, but patients can have different profiles of receptor sensitivity. In my conversations with Ms. A’s primary care physician and GI specialist, metabolic syndrome was not an issue. Clearly, low-dose olanzapine was very helpful in her treatment.
Daniel Storch, MD
Key Point Health Services
Catonsville, Maryland
References
1. Goodnick PJ, Barrios CA. Use of olanzapine in non-psychotic psychiatric disorders. Expert Opin Pharmacother. 2001;2(4):667-680.
2. Brewerton TD. Psychopharmacologic management of eating disorders. Presented at: 25th Annual National Psychopharmacology Update; February 2020; Las Vegas, Nevada. Accessed December 8, 2020. https://legacy.audio-digest.org/pages/htmlos/pastissues.html?sub1=psychiatry&sub2=2020
3. Diagnostic and statistical manual of mental disorders, 5th ed. American Psychiatric Association; 2013.
4. Brewerton TD, D’Agostino M. Adjunctive use of olanzapine in the treatment of avoidant restrictive food intake disorder in children and adolescents in an eating disorders program. J Child Adolesc Psychopharmacol. 2017;27(10):920-922.
5. Lobos CA, Komossa K, Rummel-Kluge C, et al. Clozapine versus other atypical antipsychotics for schizophrenia. Cochrane Database Syst Rev. 2010;(11):CD006633.
6. Komossa K, Rummel-Kluge C, Hunger H, et al. Olanzapine versus other atypical antipsychotics for schizophrenia. Cochrane Database Syst Rev. 2010;(3):CD006654.
7. Bachner-Melman R, Lerer E, Zohar AH, et al. Anorexia nervosa, perfectionism, and dopamine D4 receptor (DRD4). Am J Med Genet B Neuropsychiatr Genet. 2007;144B(6):748-756.
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