Early assertive pharmacotherapy intervention study for stimulant associated psychosis—a 24-month prospective randomized controlled trial

Abstract

<p><strong>Background</strong>: Both cocaine and methamphetamine are the top two commonest misused stimulants worldwide. It is well established that stimulant use can induce psychotic disorder, and a substantial proportion of stimulant associated psychosis will convert to schizophrenia. Thus, early assertive pharmacotherapy is in utmost need. Scanty evidence is available on the suitable choices of antipsychotics that can benefit both stimulant use and its associated psychosis.</p><p><strong>Aims & Objectives</strong>: This study aimed to compare the clinical outcomes from using aripiprazole or paliperidone to treatment-as-usual (TaU) in stimulant users with stimulant associated psychosis on their efficacies in treating the psychosis, stimulant dependence, and changes in mood, cognitive and functional outcomes. It also looked into the conversion rate from stimulant-induced psychotic disorder to schizophrenia after the use of early assertive pharmacotherapy among stimulant users.</p><p><strong>Method</strong>: This study was a 24-month, two phases, three-arm, prospective longitudinal interventional study. Consented stimulant users with psychotic symptoms were randomized to receive either aripiprazole, paliperidone or TaU for 12 months in the single-blinded “Active Intervention” phase, followed by another 12 months open-labelled “Observation Maintenance” phase when the allocated interventions could be continued, stopped or changed to other medications. Primary outcomes including: 24-item Brief Psychiatric Rating Scale (BPRS-24), Clinical Global Impression (CGI), Glasgow Antipsychotic Side-effect Scale (GASS), Severity of Dependence Scale (SDS), severity of DSM-5 defined stimulant use disorder (SUD), Stages of Change Readiness and Treatment Eagerness Scale-Drug (SOCRATES-D), and secondary outcomes including: Beck Anxiety Inventory (BAI), Beck Depression Inventory-II (BDI-II), Frontal Assessment Battery (FAB), Montreal Cognitive Assessment (MoCA), and Addiction Severity Index-Lite (ASI-Lite) were assessed.</p><p><strong>Results</strong>: 165 stimulant users with psychotic symptoms were randomized. At the end of the “Active Intervention” phase and the “Observation Maintenance” phase, there were no significant intervention group differences in BPRS-24, GASS, CGI-S, SDS and SUD for cocaine, SOCRATES-D, BAI, BDI-II, FAB and ASI-Lite. There could be a potential transient worsening of psychological dependence to methamphetamine when aripiprazole and paliperidone were prescribed in the first six months when compared to TaU group (p < .05). Stimulant users taking aripiprazole had better CGI-I scores (p < .001), and had mitigated DSM-5 defined methamphetamine use disorder severity when compared to the TaU group (p < .05). Stimulant users taking paliperidone showed the worst MoCA scorings (p < .05) among the three intervention groups. The prevalence of schizophrenia converted from stimulant-induced psychotic disorder was 10%.</p><p><strong>Discussion & Conclusions</strong>: Clinicians should aware that early antipsychotic pharmacotherapy can help lowering the conversion rate of stimulant induced psychosis to schizophrenia. Both aripiprazole and paliperidone were well tolerated in stimulant users with associated psychosis. Aripiprazole demonstrated significantly better clinical improvement in stimulant associated psychotic symptoms and was able to improve the severity of methamphetamine use disorder than the other two intervention groups. When paliperidone is prescribed to stimulant users with associated psychosis, their cognitive function should be monitored.</p>