Steroid Induced Mania
“WINNING IS ABOUT HEART, NOT JUST LEGS. IT’S GOT TO BE IN THE RIGHT PLACE.” – LANCE ARMSTRONG.
Mr. Neo, 77-year-old male, premorbidly well adjusted, with family history of psychotic illness in brother, with no personal past history of mental illness suddenly developed redness of face and itching all over body which he attributed to the excessive exposure to sun (sitting in sun 2-3 h daily in late winter). Considering it to be sunburn, he was given antihistaminics in the form of the tablet chlorpheniramine maleate 25 mg for 3 days, but there was no relief. Then on the advice of a pharmacist, he took tablet dexamethasone (exact dose not available) thrice daily for 4-5 days with which his signs and symptoms of skin problem improved. However, after 5 days of taking dexamethasone, he started speaking excessively, was noted to be cheerful, overactive, interact with strangers, had reduced sleep, and increased appetite. Despite sleeping for 2-3 h he would appear fresh and energetic. Later over another 3-4 days, he also developed symptoms of grandiosity, over planning and overspending. Whenever anyone would attempt to stop him, he would become irritable. By 1-week of onset of symptoms he was not manageable at home and this led to psychiatric consultation.
He was started on clonazepam 0.5 mg/day twice daily. A dermatology opinion was sought and in view of his skin lesions he was started on the tablet methylprednisolone for facial redness for 5 days with gradual tapering of steroids over next 7 days. His investigations in the form of hemogram, blood biochemistry and thyroid function tests did not reveal any abnormality.
However, with starting of methylprednisolone his symptoms of mania worsened further, and he was started on the tablet olanzapine 2.5 mg/day and titrated up to 7.5 mg/day along with the continuation of clonazepam. His skin lesions improved with methylprednisolone, and it was tapered off as per plan, but his symptoms of mania persisted even after stopping steroids. As a result of this he was continued on olanzapine and over next 1-week his symptoms resolved and all psychotropic medications were stopped.
Q. Can corticosteroids “unlock” hidden potential for mania, or are steroid-induced mood symptoms a temporary reaction? And when these mood symptoms occur, what is the best way to treat them?
Psychiatric symptoms develop in 5% to 18% of patients treated with corticosteroids. These effects—most often mania or depression—emerge within days to weeks of starting steroids.Steroid-induced symptoms emerge from 3 to 4 days to a median of 11 days after a patient starts corticosteroid therapy. After steroids are discontinued, depressive symptoms persist approximately 4 weeks, mania 3 weeks, and delirium a few days. Approximately one-half of patients with steroid psychosis improve in 4 days and one-half within 2 weeks.
Q. Who is at risk?
Psychiatric history.
Past psychiatric illness does not seem to be a risk factor for psychiatric side effects of corticosteroids, although patients with a history of post traumatic stress disorder are more likely to suffer depression while taking corticosteroids.
Corticosteroid exposure.
Patients who did not experience psychiatric side effects with corticosteroids in the past appear not to be protected if corticosteroids are used again. One report examined 17 cases of steroid-induced psychiatric illness in patients with previous exposure to corticosteroid therapy. Six patients had previous psychiatric side effects while taking corticosteroids, and 11 did not.
Age and gender.
Patient age appears unrelated to development of psychiatric symptoms after corticosteroid use. One study suggested women are twice as likely as men to develop psychiatric symptoms (77 versus 38 cases in 115 patients), but many illnesses that require corticosteroid treatment occur more frequently in women. Other researchers found a slight female predominance (58% versus 42% of cases) when they excluded patients with systemic lupus erythematosus and rheumatoid arthritis, which are more common in women than in men.
Dosage.
Higher corticosteroid dosages increase the risk of psychiatric symptoms.
Q. Medical conditions for which corticosteroids are commonly used ?
Steroids are powerful and effective drugs used to treat a variety of medical conditions. Corticosteroids, the most common group of steroids, treat arthritis, asthma, autoimmune diseases, skin conditions and some kinds of cancer. A different group of steroids, anabolic steroids, are rarely used in medicine and are more widely associated with performance enhancement and abuse in competitive athletics and weightlifting.
Q. Bipolar trigger?
Do corticosteroids’ acute psychiatric side effects have long-term sequelae? Longitudinal evidence is scarce, but a few reports suggest corticosteroids could play a role in the onset of primary bipolar I disorder.
Q. Symptomatic treatment ?
Corticosteroid-induced side effects are usually managed by tapering off the steroids and treating the psychiatric symptoms. Simply tapering off the steroids—without additional treatments—led to recovery in 33 of 36 patients. Stopping corticosteroids is not always possible or desirable, however, especially in many medically complicated cases seen by psychiatric consult services.
In a recent case, a man, age 67, on the oncology service who was receiving corticosteroids every 2 weeks as part of his chemotherapy. The patient was admitted to the hospital for acute mental status changes 2 days after his last corticosteroid dose. He had pressured speech, grandiosity, and had not slept in 2 days. We started risperidone, 1 mg bid, and most of his manic symptoms resolved within 2 days. His chemotherapy was continued without corticosteroids. If this had not been not possible, it would have been recommended continuing risperidone prophylactically.
No double-blind, placebo-controlled studies have examined prevention or treatment of steroid-induced mania or other psychiatric symptoms. Uncontrolled trials and case reports suggest benefit from some symptomatic and preventive treatments.
Treating manic and mixed mood symptoms. Twelve outpatients with manic or mixed symptoms from corticosteroid use received olanzapine in a 5-week, open-label trial. Flexible dosing started at 2.5 mg/d and was increased as needed (maximum 20 mg/d). One patient dropped out for lack of efficacy. For the others, manic and mixed symptoms improved significantly, as indicated by scores on the Young Mania Rating Scale, Hamilton Rating Scale for Depression, and Brief Psychotic Rating Scale.
Evidence from case reports indicates that lithium, carbamazepine, haloperidol, or quetiapine also can successfully treat steroid-induced manic symptoms.
Treating other psychiatric symptoms. Case reports support electroconvulsive therapy, fluoxetine, amitriptyline, lamotrigine, or lithium, for steroid-induced depression, and haloperidol or risperidone for steroid-induced psychosis.
In four cases, tricyclic antidepressants appeared to worsen corticosteroids’ psychiatric side effects. These case patients might have had steroid-induced delirium instead of mood disorders or psychosis, however, and the tricyclics’ anticholinergic effects could have worsened the delirium.
Q. Preventing steroid-induced symptoms ?
Although clear guidelines on when to start preventive treatments do not exist, potential candidates for pretreatment with lithium or other agents include patients who have developed psychiatric symptoms multiple times after repeated corticosteroid use and are at high risk if psychiatric side effects occur.
Lithium.
Prophylactic lithium was given to 27 patients with multiple sclerosis and taking corticosteroids for acute exacerbations. None developed psychiatric symptoms. At the same clinic, 6 of 44 patients with multiple sclerosis or retrobulbar neuritis developed psychiatric side effects after using corticosteroids without lithium.
Other mood stabilizers.
Two case reports describe patients who repeatedly developed manic symptoms after multiple corticosteroid doses. Carbamazepine, 600 mg qd, and gabapentin, 300 mg tid, prevented manic symptoms after additional corticosteroid pulses.
“WE HAVE TWO OPTIONS, MEDICALLY OR EMOTIONALLY: GIVE UP OR FIGHT LIKE HELL”. – LANCE ARMSTRONG.