Introduction

Clozapine, an atypical antipsychotic agent, offers reduced extrapyramidal side effects and is indicated for the treatment-resistant schizophrenia population. Worrisome side effects of clozapine include sedation, hypersalivation, constipation, seizures, weight gain, hyperglycemia, hyperlipidemia, and agranulocytosis [1],[2]. Many psychotropic medications, including antipsychotic agents, are associated with significant weight gain. Allison et al. [3] performed a meta-analysis and estimated the average weight change for subjects treated with antipsychotic agents over a 10-week period ranged from 0.39 Kg reduction with molindone to 4.15 Kg and 4.45 Kg increase with olanzapine and clozapine, respectively.

Weight gain, a significant concern in clozapine-treated patients, may continue for up to 46 months after clozapine-initiation [1],[2]. Several studies have reported substantial weight gain with clozapine [4, 5, 6, 7, 8, 9] which significantly correlated with clinical response in two studies [6],[9]. Obesity is associated with an increased risk for hypertension, dyslipidemia, insulin resistance; type 2 (non-insulin-dependent) diabetes mellitus, cardiovascular disease, respiratory dysfunction, and gallstones [10].

Modafinil is a schedule IV wake-promoting agent, which is FDA-approved for the treatment of narcolepsy. It is chemically and pharmacologically distinct from other psychostimulants. Modafinil does not appear to have the same dopaminergic activation or cause jitteriness, anxiety, or involuntary movements that are routinely seen in other CNS stimulant drugs [11]. Additionally, modafinil has a low potential for abuse [12, 13, 14, 15]. Mild headache and nausea are the two most frequently observed adverse experiences with modafinil [11]. The wake-promoting mechanism of action of modafinil remains uncertain, despite numerous reports of its neuropharmacological action in the brain [14, 15, 16].

Modafinil may be useful in relieving the sedating and fatiguing side effects of other medications such as clozapine; however, significant weight loss is not an expected outcome. We present a case of modafinil-associated weight loss in a clozapine-treated male with schizoaffective disorder.