Abstract
To the Editor
There is emerging evidence to suggest that downregulation in gamma-aminobutyric acid (GABA) neurotransmission may be involved in the expression of schizophrenia (Guidotti et al., 2005). Given this, pharmacological agents that enhance GABAergic signal transduction may have potential therapeutic benefits in the treatment of schizophrenia. We describe a case where GABAergic mechanisms are likely implicated in the clinical presentation and outcome of a patient with schizophrenia.
Ms S is a thirty-nine year old woman who had been diagnosed with schizophrenia ten years ago. At the time of presentation she had been on clozapine for eight years. On therapeutic doses of clozapine 200mg daily her condition had been in remission. However, she had been episodically non-compliant with clozapine and on four previous occasions in the immediate period following clozapine cessation, the patient developed florid psychotic symptoms in the form of persecutory, grandiose delusions, disorganised behaviour and auditory hallucinations. She also displayed catatonic features (Bush Francis Catatonia rating scale of 20 indicating severe catatonia) with excitement, mutism, posturing, staring, negativism and echolalia. Each of these episodes required closed ward management and on every occasion, the patient’s symptoms resolved following reinstitution of clozapine. Of note, there was no history of catatonia prior to clozapine commencement.
Given the history of clozapine non-compliance and the episodes of clozapine withdrawal psychosis with catatonia, the patient was commenced on a combination of risperidone depot and lorazepam, which resulted in a partial remission of her psychosis and no catatonic symptoms.
During her admission lorazepam 2mg was ceased and within 48 hours she developed acute psychosis with catatonic features, identical to that, which occurred following clozapine withdrawal. The deterioration in mental state required closed ward management. Lorazepam was recommenced with significant reduction of psychotic symptoms and complete resolution of catatonia. Over the next seven months, and on a further four separate occasions, lorazepam 2mg was ceased. On each occasion, within 48 hours the patient became floridly psychotic with marked catatonia
Given the above presentations following lorazepam withdrawal, the patient was maintained on risperidone depot and regular lorazepam. She was successfully discharged home on this combination with partial resolution of psychosis, no catatonic symptoms and adequate functioning.
This case initially described a patient who presented with clozapine withdrawal psychosis. This has been previously well described (Moncrieff, 2006). However, the patient also had accompanying clozapine withdrawal catatonia which is less well-recognised and poorly understood (Bastiampillai et al., 2009), especially when in association with clozapine withdrawal psychosis. One possible explanation is that clozapine, along with its other mechanisms of action, potentiates GABA (Bragina et al., 2007; Marx et al., 2011). The association between clozapine and GABA is suggested in our case by the fact that catatonia is well known to be linked with GABA dysregulation (Northoff, 2002) and that the patient developed a similar psychosis with catatonia following withdrawal of lorazepam, a benzodiazepine that potentiates GABA. While lorazepam withdrawal catatonia has previously been described (Manjunatha et al., 2007), this patient also experienced lorazepam withdrawal psychosis – a clinical presentation that has not been reported.
In this case, given the similar clinical presentations for clozapine and lorazepam withdrawal, we hypothesise that GABA dysregulation may be involved in the development of psychosis with catatonia in susceptible patients with schizophrenia. This case suggests that clozapine may potentiate GABA; and clozapine withdrawal psychosis and clozapine withdrawal catatonia may be associated with downregulation of GABA receptors. This potential link between GABA dysregulation and clozapine withdrawal psychosis has not been previously postulated and possibly has important clinical implications. In addition, GABAergic agents such as lorazepam may have specific antipsychotic effects in a subset of patients in addition to relieving catatonia. Given this, clinicians should be aware that some patients could experience a relapse of psychosis with catatonia when clozapine or lorazepam are withdrawn.