Pregabalin Adjuventia Helped Risperidone-Induced Extrapyramidal Syndrome and Augmented Antipsychotic Response in an Adolescent with Schizophrenia

Abstract

Here, authors report on an interesting case of early-onset of schizophrenia where adjunctive pregabalin alleviated risperidone-induced pseudoparkinsonism, helped with insomnia and agitation and boosted antipsychotic response with great tolerability. We wager that gabapentenoids can be a viable option in the niche of psychopharmacotherapy of schizophrenia in CAP population.

Case Vignette

A 17-year-old male Lebanese boy was brought in to hospital by his parents for scholastic drop and erratic behaviour. This had a one year history of gradual onset of social shrinkage, neglected personal hygiene, fitful sleep, scholastic underachievement, digressive speech and occasional ill-founded giggling. This ran a progressive course with reported muttering under breath, awkward gait and a caricatured facial demeanor.

Patient was the only child of a monogamous consanguineous family. He had normal developmental milestones. A family history was positive for a maternal aunt with schizophrenia on clozapine. There was no medical history of relevance, or known drug allergies nor a history of trauma, seizures or abuse. No history of illicit drug use, or ongoing legal problems was reported. Mental state examination revealed a lanky habitus, tousled, shabby appearance, fleeting eye contact, attitude d’impénétrabilité, a bit agitated, slavering, ungrounded laughter, disjointed, gibberish speech, restricted and at times incongruous affect, formal thought disorder and hallucinatory attitude- a picture reminiscent of dilapidated hebephrenics.

Baseline lab workup and MRI brain were within all within normal. Urine drug screen was negative. Patient was commenced on risperidone, uptitrated to 3 mg on 2 divided doses over a couple of weeks. At Wk-3, some tangible improvement was noticed in disorganized symptom domain in tandem with BPRS weekly scores. But, sleep was still fragmented and bouts of agitation were frequently noted. Dose was escalated up to 4 mg/d. At Wk-5, there was much better improvement in positive domain but he started to have bilateral acral tremors and muscle stiffness. Risperidone-induced pseudoparkinsonism was entertained and procyclidine 5 mg/d on 2 doses was prescribed. Unfortunately, patient could not tolerate anticholinergic effects of procyclidine. Neurological consult was summoned and pregabalin 75 mg bid was suggested. At Wk-7, tremors totally abated, with better motoric agility. Strikingly, sleep improved and agitation markedly diminished with the patient kept exponentially improving. This was ascribed to be non-specific effects of pregabalin. At Wk-10, per neurologist direction, we attempted to taper off pregabalin, but, lo and behold, the patient started to show psychotic decompensation with recrudescence of tremors. Pregabalin was resumed outright; tremors disappeared with attenuation of psychotic symptoms. Follow-ups at Wk-12, 16 and 20 demonstrated plateau improvement with no EPS. Pregabalin appeared to counteract EPS of risperidone meanwhile helped with insomnia, agitation and above all augmented antipsychotic response. This was achieved with great tolerability. We opine that gabapentenoids, like pregabalin in this case, might be a viable option to augment antipsychotic response and mitigate neurologic side effects in CAP population.

Discussion

Early-onset schizophrenia (EOS), with an onset prior to age of 18 year are generally notorious to have poor prognostication with male preponderance, heavy genetic load, soft neurologic signs, incipient onset, negative and cognitive domain presentation, and poor antipsychotic response.¹ Atypical antipsychotics are first-line for EOS on guidelines.

Pregabalin is anticonvulsant, gabapentenoid, a GABA analogue, binds selectively to α-2 δ-1 subunit of Ca channels, renally-cleared that has been used off-label in psychiatry for a multitude of indications including, inter alia, generalized anxiety disorder, social anxiety disorder, alcohol use disorder, alcohol/benzodiazepine withdrawal, and bipolar mood disorder.² Here, we reported a case of EOS, that favorably responded to risperidone but incurred an EPS in form of pseudoparkinsonism for which procyclidine could not be tolerated. Pregabalin adjuventia successfully alleviated EPS, helped with concomitant agitation and insomnia and surprisingly, augmented antipsychotic response. We postulate GABA potentiation by pregabalin boosts dopamine blockade in mesolimbic pathway and attenuates serotonergic tone to mesocortical pathway.³ This goes hand-in-hand with hypothesized GABA deficiency underpinnings of schizophrenic neurobiology. It was achieved with high tolerability. We conclude that pregabalin can be an attractive augmentative strategy to the psychopharmacological armamentarium of schizophrenia.

Similarly, Gabriel⁴ has conducted an open-label pilot study of successful add-on gabapentin in schizophrenia partial responders. Demily⁵ et al. reported effective use of gabapentin in ultra-resistant schizophrenia with aggressive behaviour. We have previously reported on a case of early-onset of schizophrenia where adjunctive gabapentin alleviated paliperidone head tremors and boosted antipsychotic response.⁶

Englisch⁷ et al. found pregabalin both effective and tolerable in schizophrenia.