A group of patients with melancholic depression do not respond rapidly to a single antidepressant and sometimes even look worse with selective serotonin reuptake inhibitors (SSRIs). Described here is a method to treat patients who have melancholic depression rapidly with few side effects.
An 80-year-old man presented with penile pain of 6 months' duration associated with decreased interest, energy, appetite, weight (20 pounds), sleep, and concentration. He would not dress or go outdoors. He was preoccupied with his pain and felt no enjoyment. He had numerous medical consultations and had taken gabapentin and paroxetine hydrochloride, which induced severe anxiety, clonazepam, and carbamazepine. He denied a prior history of depression but later admitted to two earlier major depressions. A mental status examination revealed an extremely anxious man with psychomotor slowing, lying almost prostrate in a chair trying to keep his clothes from touching his penis. There was no evidence of hallucinations or delusions. His memory appeared to be intact.
His laboratory data, including an SMA, B12, folate, urinalysis, and thyroid-stimulating hormone, were within normal limits. His serum sodium was 128 mmol /L. The results of a computerized tomography scan of his head and pelvic area were normal. An electroencephalogram yielded normal results. He had a history of several myocardial infarctions and angina. His medications included terazosin hydrochloride, Captopril, isosorbide dinitrate, digoxin, carbamazepine, and clonazepam.
Premorbidly, he was described as a dapper, social salesman.
Initially, a 2-day taper and discontinuation of carbamazepine was begun. Venlafaxine hydrochloride (12.5 mg/d), divalproex sodium (125 mg twice a day [bid]), and risperidone (0.5 mg/d) were started. Four days later the patient was reevaluated and found to have a decrease in anxiety, pain, and dysphoria. He had begun to eat and admitted to two mornings where he was pain free. Two weeks later he felt strong, had gained 4 pounds, and was driving a car. His dose of venlafaxine hydrochloride had been increased to 12.5 mg bid, and his dose of divalproex sodium was raised to 125 mg/d four times a day. Four months later he said he felt too aggressive, so the venlafaxine hydrochloride was reduced to 12.5 mg/d. While taking this regimen he had some mild mood swings, so gabapentin 100 mg three times a day was added. He has remained well for 6 months.
An 85-year-old woman presented with severe anxiety, weight loss (HO pounds during 4 years), constant nausea, no energy or interest, and refusal to get out of bed, bathe, or walk. She admitted to being depressed for the past 18 months, having no desire to live or to eat. She complained of pain behind her left eye and headaches. Her current weight was 85 pounds. She had become confused and violent while taking lorazepam and alprazolam. A trial of paroxetine hydrochloride resulted in severe agitation.
Her major problems began with a cerebrovascular accident (CVA) during a heart catheterization, resulting in a left pontine infarction and a partial right hemiparesis. Subsequently, she had two more CVAs, recovering from the last two. She had labile hypertension, diabetes mellitus, recurrent diverticulitis, constipation, frequent impactions, arthritis, and osteoporosis. Her medications included levothyroxine sodium, ticlopidine hydrochloride, pravastatin sodium, and Lisinopril. Insulin had been discontinued because her blood sugars had normalized. The results of baseline laboratory tests were within the normal range.
On examination she was oriented times three. She appeared emaciated and unkempt. She admitted to sleep disturbances, anxiety, and a desire to die. There was no evidence of hallucinations or delusions. Her immediate and recurrent memory were moderately impaired.
Venlafaxine hydrochloride (12.5 mg/d) and divalproex sodium (125 mg bid) were begun. The patient became sedated and less anxious but was nauseated. Risperidone (0.5 mg/d) was begun and divalproex sodium was reduced to 125 mg/d.
With this regimen, the patient began to sleep and eat by the third day of treatment. Her anxiety and dysphoria improved. Two weeks later she appeared in the office with makeup on and was neatly dressed. However, she still had little energy or interest.
Roose et al.1 found that few elderly, agitated, depressed patients responded well to SSRIs, but that they did respond to tricyclics that are 5-HT2 blockers. The atypical antipsychotics, which are 5-HT2 blockers, also have an activating antidepressant property and have been found to rapidly enhance the SSRIs.2 This is a possible mechanism for the rapid response. Divalproex sodium seems to reduce the anxiety and stop any mood swings.
Although it is possible that higher doses of venlafaxine hydrochloride or some other dual action antidepressant might bring about the same response, the fragility of these patients makes this a combination that should be studied.
1. Roose SP, Glassman AH, Attia E, Woodring S. Comparative efficacy of selective serotonin reuptake inhibitors and tricyclics in the treatment of melancholia. Am J Psychiatry, 1994;151:1735-1739.
2. Shelton R, Tollefson G, Tohen M, et al. The study of olanzapine plus fluoxetine in treatment-resistant major depressive disorder without psychotic features. Presented at the 38th Annual NCDEU Meeting; Boca Raton, Florida; June 10-13, 1998.