Risperidone for successful treatment of postictal psychosis refractory to olanzapine

Abstract

Postictal psychosis (PIP) in patients with epilepsy is often mistaken for other primary psychiatric disorders. Depending on its severity, PIP often prompts empiric treatment with atypical antipsychotics, which are balanced against the risk of lowered seizure thresholds. Here we present a case of olanzapine-resistant PIP, where risperidone was used as a safe and effective abortive treatment.

Psychosis temporally related to epilepsy is increasingly recognized as a distinct clinical entity. Of its variants, postictal psychosis (PIP) was reported in a 1950s case series as most common, representing 25% of epilepsy-related psychoses.¹ Still, a lack of established diagnostic criteria and management strategies renders PIP challenging to identify or treat. Although often PIP resolves spontaneously within a week, empiric management may reduce morbidity, as severe PIP can manifest with harm to self or others.² Prior reports demonstrated the utility of atypical antipsychotics such as olanzapine³ and quetiapine⁴ in PIP. Here we present a case of olanzapine-resistant PIP successfully treated with risperidone.

CASE PRESENTATION

A 30-year-old man with traumatic brain injury 7 years earlier complicated by generalized tonic-clonic (GTC) seizures on long-term oxcarbazepine presented for evaluation. Four days before admission, the patient ran out of oxcarbazepine and instead took leftover valproate that had been discontinued 1 year earlier due to side effects. Three days before admission, he went to bed and awoke 36 hours later on shattered glass, with confusion, diffuse soreness, and lacerations. He also began hearing hockey commentary and the Canadian anthem, which he surmised were auditory hallucinations.

On arrival, the patient reported tongue pain, diffuse myalgias, and ongoing auditory hallucinations. He denied weakness, sensory changes, or visual or auditory command hallucinations. His medical history was notable for migraine with aura and anxiety, with no history of mania, hypomania, or depression. His only medication was oxcarbazepine, with no known drug allergies. He endorsed consuming 10 alcoholic drinks a week, daily cannabis, and intermittent cocaine use, most recently 1 month earlier, and denied tobacco use. He obtained his cannabis solely from a medical dispensary and denied illicit substance ingestions such as K2. There was no family history of psychosis. Review of systems revealed a prior episode of postictal auditory hallucinations during an emergency room presentation following a seizure that was not known to the emergency room care team at the time.

Vital signs included a blood pressure of 143/82 mm Hg and were otherwise within normal limits. The patient appeared mildly diaphoretic, inattentive, and anxious with continuous pacing; he reported ongoing auditory hallucinations and did not exhibit negative symptoms of psychosis. He had a 2-cm left-sided tongue laceration and healing lacerations over his extremities, trunk, and face (Figure 1).

Figure 1.

The patient’s lacerations on his (a) tongue and (b) extremities.

Laboratory studies were notable for an alanine transaminase of 473 U/L, aspartate transaminase of 2056 U/L, and creatine kinase of 39,750 U/L. Urinalysis showed 2+ ketones, 2+ blood, and no red blood cells. Hepatitis B surface antigen and hepatitis C antibody were negative. Ethanol was undetectable. Toxicology was positive for tetrahydrocannabinol, oxcarbazepine, and valproate and negative for amphetamines, cocaine, benzodiazepines, and lysergic acid diethylamide. Computed tomography of the head without contrast showed unchanged encephalomalacia from remote trauma involving the bilateral frontal and bilateral anterior temporal lobes. Spot electroencephalography revealed no epileptiform discharges.

The patient received intravenous fluids and 4 mg lorazepam per Clinical Institute Withdrawal Assessment for Alcohol. In addition to restarting his home oxcarbazepine, he was started on olanzapine with haloperidol as needed. Overnight his auditory hallucinations persisted, and he developed new visual hallucinations. The patient became increasingly restless, removing his intravenous lines twice, but fell asleep after receiving 1 mg intravenous haloperidol. On the second day, neurology and psychiatry were consulted given persistent hallucinations. Antipsychotics were transitioned to oral risperidone 1 mg daily. Auditory and visual hallucinations resolved later in the day, with noticeable improvement in attention, restlessness, and sleeplessness. Given his creatine kinase rapidly declined and his hallucinations were well controlled, he was discharged on the third day of admission with a plan to complete a 1-week course of risperidone.

DISCUSSION

With this case presentation, it was felt that the patient likely suffered breakthrough GTC seizures over 36 hours as a result of antiepileptic drug nonadherence, supported by significant lateral tongue biting. He likely sustained body lacerations from convulsions over broken glass, and rhabdomyolysis due to convulsions and interval immobilization. The differential remained broad in suspected PIP—including alcohol withdrawal, brief psychotic disorder, substance-induced psychosis, and mood disorder with psychotic features—but his presentation and response to treatment were otherwise most consistent with PIP. This was further corroborated by marijuana solely sourced from a medical dispensary, minimizing the likelihood of contaminated or synthetic marijuana (e.g., K2) contributing to hallucinations.

There remains a need for evidence-based management of PIP. Case reports describe olanzapine³ and quetiapine⁴ as efficacious treatments, but they are balanced against lowered seizure thresholds. Additionally, it is not known how pharmacologic management changes long-term outcomes, such as PIP recurrence or progression to a primary psychotic disorder. Interestingly, the patient reported a prior episode of breakthrough GTC seizures with auditory hallucinations hours later, unknown to his care team then. Although the auditory hallucinations spontaneously resolved within a week, this highlights the importance of inquiring about hallucinations in postictal patients for a thorough review of systems.

During this admission, the patient’s auditory hallucinations not only persisted after a dose of olanzapine, but also progressed to concomitant, first-time visual hallucinations. Because olanzapine reaches peak concentration in 6 hours,⁵ the patient’s PIP was likely resistant to olanzapine. In transitioning his antipsychotic medication, risperidone was felt appropriate due to its lowest risk of seizures among the atypical antipsychotics⁶ and peak concentrations that are reached in 1 hour.⁵ All hallucinations rapidly resolved following addition of oral risperidone to his regimen of oxcarbazepine, without further seizure activity noted. Given this dramatic temporal response, it was unlikely that the hallucinations resolved solely as a function of natural history following his seizure.

To our knowledge, this is the first reported case of PIP initially resistant to atypical antipsychotics. While both risperidone and olanzapine belong to the same pharmacologic class, olanzapine’s broader receptor-binding profile may account for observed differences in response. Additionally, cytochrome P450 2D6 and 3A4, responsible for generating active metabolites of risperidone, are mediators of olanzapine clearance.⁵ While the determinants of resistance remain unknown, in this case they may bear relevance to the patient’s atypical presentation. Classic PIP often involves a lucid interval between the last seizure and onset of mental status changes. Mania, depressed affect, grandiose delusions, or aggression are usually seen, whereas hallucinations are less common.⁷ Additionally, in light of its diagnostic difficulty, Logsdail’s proposed criteria have been frequently cited:

1. PIP occurs within 1 week of a seizure or cluster of seizures.

2. PIP lasts 24 hours to 3 months.

3. Mental status change is characterized by delirium, hallucinations, or delusions.

4. There is no evidence of antiepileptic drug toxicity, psychosis in the past 3 months, electroencephalogram suggestive of nonconvulsive status, recent head injury, alcohol intoxication, or drug intoxication.⁸

The patient’s presentation was atypical due to dual auditory and visual hallucinations and an absent lucid interval, though he endorsed a prior episode of PIP with lucid interval. He also deviated from the observed delay between epilepsy onset and first episode of PIP of 13.1 to 21.7 years, as described in the literature, in contrast to 6 years here.⁹ The patient did not strictly satisfy Logsdail’s criteria given positive toxicology for tetrahydrocannabinol, though it was believed to be less likely of a trigger for his seizure given chronic daily use. Going forward, sufficiently powered studies will be necessary to quantify risk factors for PIP and to compare outcomes between pharmacologic and conservative management. This will likely require broadened inclusion criteria than those historically used.