History and examination

This case presents a male military veteran in his 20s with schizoaffective disorder and cannabis use disorder who presented with acute exacerbation of psychosis in the context of daily cannabis use. History of substance use is important to ascertain from a patient, as it can mimic other mental disorders. The patient was discharged from the military 6.5 months earlier, after two years of service, with two previous psychiatric hospitalizations. During his prior hospitalization, he was diagnosed with schizoaffective disorder. The patient denies other medical conditions. Family history is significant for bipolar disorder in his mother. Previously, the patient had trials of lithium, divalproex, risperidone, and olanzapine without adequate control of his psychotic symptoms (Table 1).

At the beginning of his hospitalization, following direct transfer from another hospital, the patient presented with visual hallucinations characterized by hyper-religiosity, including ritualistic behaviors and self-reported communication with supernatural entities. He experienced extreme mood lability with episodes of agitation and aggression, including physical aggression towards objects and verbal aggression directed towards others, that were clearly distressing to him, fluctuating with periods of calmness. His symptoms were noted to have started soon after discharge from the military and preceded Cannabis sativa use, but appeared to worsen following his initial hospitalization. 

Differential diagnosis

Patients presenting with recent intoxication of a substance, either acutely or chronically, with concomitant psychotic symptoms are challenging. When evaluating patients with psychotic symptoms, it is important to consider whether the potential underlying cause is due to an independent psychotic disorder, substance use, or a psychotic disorder exacerbated by substance use. In these clinical situations, it is important to maintain a high suspicion of substance-induced psychotic disorders. Substance-induced psychotic disorders are within the Schizophrenia Spectrum and Other Psychotic Disorders category of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) and can occur with various substances of abuse [1]. When considering schizophrenia or schizoaffective disorder in the context of substance use, effort must be made to determine the duration and circumstances of the symptoms. Substance-induced psychotic disorders can be differentiated from independent psychotic disorders if the symptoms persist longer than one month after severe intoxication or cessation and acute withdrawal, or if the symptoms are known to have preceded the usage of substances [1]. Once suspicion of an independent psychotic disorder is established, investigation must be made to delineate the psychotic symptoms’ characteristics, including frequency and history, as well as the presence of mood symptoms, such as a major depressive, manic or mixed episode. In this case, when considering the potential underlying causes of the patient's acute psychosis, we discussed cannabis intoxication. This diagnosis was not supported due to the lack of intact reality testing with concurrent visual hallucinations, as our patient was unable to differentiate internal stimuli from external stimuli and environment [1]. While our patient was using cannabis daily, upon further evaluation of history, presence of mood symptoms, and duration of the symptoms, it was determined that symptoms preceded cannabis use. In this case, diagnosis remained consistent with schizoaffective disorder given the presence of hallucinations and delusions for more than two weeks in the absence of major mood symptoms [1].

Treatment

This patient had previous trials of lithium, divalproex, risperidone, and olanzapine without adequate control of psychotic symptoms. Prior to admission, in the past, he had been treated with oral risperidone, and completed two loading doses of paliperidone long-acting injectable (LAI), a metabolite of risperidone. There is a possibility he may have been non-compliant with his medications in the past as medication level monitoring performed during hospitalizations in the past revealed subtherapeutic levels. Upon admission, divalproex dosage was increased from 500 milligrams (mg) twice per day (BID) to 1000 mg BID. The valproic acid (VPA) level was 114 mcg/ml (reference range: 50 - 100 mcg/ml). Divalproex was decreased to 750 mg BID to bring VPA level within the therapeutic range at 99 mcg/ml (reference range: 50 - 100 mcg/ml). During this time, he was also taking risperidone orally in conjunction with the paliperidone LAI and divalproex. The risperidone was increased to 4 mg daily at night (qhs) until the first maintenance dose of paliperidone was administered, then risperidone was discontinued. He received the first scheduled maintenance dose of paliperidone 234 mg based on his loading dose timing, within four weeks. Following this, the patient’s mood continued to fluctuate, and residual psychosis consistent with symptom pattern prior, persisted beyond that compatible with his stated goals. Despite the evidence suggesting clozapine would be effective given the resistant nature of this patient’s disorder, the patient and next of kin were unable to provide consent for clozapine due to concerns for frequent monitoring. This presented a unique situation of managing residual psychosis in a patient who is already taking one antipsychotic medication. The patient demonstrated tolerability and response to as-needed haloperidol for rapid symptom reduction. Upon further discussion with the patient and his next of kin, the team decided to initiate and titrate haloperidol. Haloperidol was introduced at a low dose and carefully titrated to 2 mg BID within three days to optimize therapeutic response and minimize potential side effects. The haloperidol was initiated approximately two days following the maintenance dose of paliperidone LAI. He responded well to this dosage of haloperidol and continued improving over a nine-day period. He was able to discuss his future goals, did not respond to internal stimuli, demonstrated insightfulness into his circumstances, and expressed his emotions and feelings in a calm manner. Literature has shown peak plasma concentrations of paliperidone palmitate once monthly are achieved with a median of 13 days post-injection [8]. Given the rapid improvement following haloperidol, with continued improvement following, we attributed the effects to the addition of haloperidol. The patient was discharged on paliperidone LAI 234 mg every four weeks, haloperidol 2 mg BID, and divalproex 750 mg BID with plan for outpatient follow-up. Complete metabolic panel was checked on follow-up with liver function values within normal limits. 

Outcome 

During hospitalization, the patient did not experience any side effects or extrapyramidal symptoms from his medications. Abnormal Involuntary Movement Scale (AIMS) completed prior to discharge was 0. He experienced resolution of distressing psychotic and mood symptoms with return to premorbid levels of functioning. He felt better equipped to pursue his goal of completing higher education with his G.I. bill, benefits available as the Servicemen’s Readjustment Act to assist American military veterans. While he declined specific substance use disorder treatment, he planned to abstain from cannabis, continue treatment and follow up with an outpatient psychiatrist.