LAUSR

Aripiprazole is an atypical anti-psychotic with partial agonism at D2, 5-HT1a, and inverse agonism at 5-HT2a, 5-HT2c [1] Being a partial D2-agonist, it is theoretically less likely to cause extrapyramidal effects. In its initial years, it was a first-choice anti-psychotic, particularly in Parkinsonism patients. We present a case of bradykinesia-predominant Parkinsonism which developed with aripiprazole-pregabalin therapy. A 50-year-male with diabetes and rheumatoid arthritis (RA) presented with gradually worsening slowness of gait and speech, and difficulty in walking, of 1.5–2 months duration. Around 4 months back, he had been diagnosed with steroid-induced psychosis. His prescription for the past 3 months included metformin 500 mg b.i.d, methotrexate 15 mg weekly, and aripiprazole 10 mg daily. He had also been on pregabalin 75 mg/day for the past 2 months for neuropathic pain. Drug or substance abuse, psychosis or depression in the past, significant family history was absent. The patient did not complain of fever, falls or forgetfulness. At presentation, he was oriented and with stable vitals. Hypomimia and hypophonia were observed. He had marked bradykinesia and decreased arm swing while walking (Video 1) but no tremors or peripheral rigidity. Routine blood investigations and magnetic resonance imaging of the brain were non-contributory. Aripiprazole-induced Parkinsonism was suspected, and its dose was reduced to 10 mg every alternate day. Significant improvement in bradykinesia was observed over 10 days and aripiprazole was discontinued. Parkinsonian features disappeared by 3 weeks (Video 2). A score of 8 on the Naranjo scale implied a ‘probable’ association between aripiprazole and Parkinsonism. Association was ‘probable’ using WHO-UMC scale of causality assessment too. The patient has been on regular follow up for the past 9 months, with an uneventful course. It is believed that ≥ 78% occupancy of D2 receptors is usually required for anti-psychotic drugs to produce extrapyramidal adverse effects. This level of occupancy is achieved readily with typical antipsychotics at the therapeutic dose. Aripiprazole on the other hand exerts 25% dopaminergic receptor stimulation and requires a greater fraction (85–90%) of receptors to be occupied to produce EPS [2]. The claim that ‘partial dopamine agonism’ would keep the drug free of EPS was the sole basis of the launch of aripiprazole. There are disparate opinions among practitioners regarding its propensity to cause Parkinsonism. Whereas some believe Parkinsonian features are common with aripiprazole, others opine that a strong association cannot be made since patients are simultaneously taking other neurological drugs. The confusion is exemplified by the removal of aripiprazole from the Beers’ preferred drugs list of elderly pharmaco-therapy. We conducted a PubMed search of published English-language case reports of Parkinsonism or related symptoms with aripiprazole. Although many case reports were found, most had limitations such as prior or concomitant use of other anti-psychotic drugs, history of substance abuse and use of anti-Parkinsonian drugs for treatment (Table 1). Only two reports had strong evidence. One involved a 32-year female with diabetes and bipolar disorder, and another was a case of a 59-year male with motor tics [3–9]. We also conducted a PubMed search using keywords ‘pregabalin’ and ‘Parkinsonism’ and could find two case reports Electronic supplementary material The online version of this article (https ://doi.org/10.1007/s1376 0-020-01370 -x) contains supplementary material, which is available to authorized users.