Letters to the Editor
Parkinsonism and Elevated Lactic Acid With Sertraline
Dear Editor: A few reports of sertraline-induced akathisia and dystonia are available, but reporting on sertraline-induced Parkinsonism is negligible (1). We report a case of Parkinsonism associated with sertraline use. To our knowledge, this is the first case in the literature to highlight a possible relation between selective serotonin reuptake inhibitors (SSRIs) and lactic acid metabolism.
Case Report
Mrs L, aged 45 years, is a married, middle-class housewife. She was premorbidly well adjusted and had no significant psychiatric or medical history and no significant family history. She presented with a 2-month history of persistent sadness, frequent crying spells, suicidal ideation, agitation, feelings of hopelessness and worthlessness, disturbed biological functioning, and weight loss of 5 kg. Her illness was precipitated by severe financial losses in her husband’s business. Moreover, he had taken a large loan to start his business, and his creditors were demanding payment. Their visits to the home caused her to become markedly restless and apparently unresponsive to her surroundings for periods of 30 minutes to 2 hours. She emerged from these spells when cold water was sprinkled on her face. Mrs L was hospitalized in a private nursing home and given tablet alprazolam 0.5 mg daily and intravenous fluid with parental B complex. She was later referred to our hospital, where all medication was discontinued on admission. She was diagnosed with major depression with conversion disorder and was started on sertraline 50 mg daily and clonazepam 1 mg daily. We increased her sertraline to 100 mg daily on the fourth day of admission. The next day, she developed excessive salivation, mask-like facies, bradykinesia, cogwheel rigidity, tremors of both hands, and monotonous speech. We immediately discontinued sertraline, and she was given intramuscular promethazine 50 mg, with partial response. We sought the opinion of a neurologist on the same day, and Mrs L was given a diagnosis of possible sertaline-induced Parkinsonism. According to the Extrapyramidal Symptom Rating Scale (2), her Parkinsonism was moderately severe. We started her on trihexyphenidyl 2 mg daily, increased to 6 mg daily over a period of 7 days. She was maintained on this dosage for 10 days, and her extrapyramidal symptoms (EPS) fully remitted. However, when trihexyphenidyl was tapered to 2 mg daily, the Parkinsonism symptoms reappeared. We therefore increased the dosage of trihexyphenidyl back to 6 mg daily, with successful results. Because her symptoms reappeared, she was investigated thoroughly. Magnetic resonance imaging (MRI) of the head revealed bilateral basal ganglia focal hyperintensities without any specific lesion. She had a normal biochemical profile for blood sugar, urea, serum creatinine, calcium phosphorus, and alkaline phosphatase. Her serum lactic acid at rest, taken on day 12, was 26.0 mg%. Because of her MRI report and raised lactic acid level, we suspected possible mitochondrial cytopathy; hence, a muscle biopsy was performed. All these investigations were carried out during the reappearance of her Parkinsonism symptoms. A histopathological study of the muscle did not reveal significant pathology, including the existence of ragged fibres. A repeat serum lactic acid level, taken at a 2-week interval, was 24 mg%. Although Mrs L’s EPS improved, she continued to have the same psychiatric symptoms. We therefore added dothiepin hydrochloride on the fifth week of admission, and gradually increased this medication to 75 mg daily. A third serum lactic acid level test, taken 2 weeks after the last sample, was 16.00 mg%. The trihexyphenidyl was gradually weaned over 2 weeks without recurrence of the Parkinsonism symptoms. Mrs L continued to take dothiepin hydrochloride for the next 4 months. Her subsequent serum lactic acid levels were 13 mg% and 12 mg%.
Most earlier case reports have not attempted to uncover underlying mechanisms for antidepressant-induced EPS. Although her MRI head scan showed no structural abnormalities in the basal ganglia, our patient developed Parkinsonism along with elevated serum lactic acid after the use of sertraline. This could be coincidental, or possibly, use of sertraline unveiled the Parkinsonism. Mrs L’s elevated serum lactic acid levels later returned to normal. Lactic acid is the end product of pyruvate metabolism. Under physiological conditions, lactic dehydrogenase converts lactate to pyruvate, which is metabolized through the citric acid cycle. An elevated lactic acid level may imply a disturbance in mitochondrial oxidative metabolism. Mrs L’s elevated lactic acid correlated clinically with her Parkinsonism symptoms. The reversible elevated lactic acid level in this case is perhaps attributable to reversible disturbances in the mitochondrial oxidative metabolism. However, Mrs L’s muscle biopsy report was normal, which suggests neither mitochondrial encephalopathy nor disturbances in the oxidative metabolism (3). This case report shows that Parkinsonism can occur with sertraline therapy, although it may be a rare side effect.
References
1. Leo RJ. Movement disorders associated with the serotonin selective reuptake inhibitors. J Clin Psychiatry1996;57:449–54.
2. Chouinard G, Ross-Chouinard A. Extrapyramidal Symptoms Rating Scale (ESRS). Can J Neurol Sci 1980;7:33–43.
3. Di Mauro S, Schon EA. Mitochondrial DNA and diseases of the nervous system. The spectrum. Neuroscientist 1997;4:53–63.
DN Mendhekar, MD, DPM
RP Benuiwal, MD
V Puri, MD, DM
New Delhi, India
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