First-Episode Psychosis Possibly due to Roxithromycin-Related Inhibition of Metabolization of Tetrahydrocannabinol
The etiology of psychotic disorders is not sufficiently understood. Current vulnerability/stress models suggest a multifactorial pathogenesis including genetic, neurobiological, social, and environmental factors.1,2 A significant body of epidemiological evidence has linked psychotic symptoms with both acute and chronic use of cannabis,3,4 making cannabis use one of the most important environmental risk factors for the development and maintenance of psychotic symptoms.1 Although the underlying mechanisms are still uncertain, it has been proposed that the major psychoactive ingredient of cannabis, δ-9 tetrahydrocannabinol (THC), may induce disruption of the endogenous cannabinoid system and affect dopaminergic neurotransmission, thereby promoting the emergence of psychotic symptoms.5,6 However, psychosis is not an inevitable consequence of cannabis use. Additional risk factors may be necessary to trigger the onset of first-episode psychosis in patients with chronic cannabis use.1 Here, we present the case of a male patient with chronic cannabis use who developed a late-onset first-episode psychosis after antibiotic treatment with roxithromycin.
The 54-year-old male patient admitted himself to our clinic and reported that conditions in his hometown have changed dramatically and he has the feeling of being pursued. He reported that his wife tried to poison him and that she was conspiring against him; subsequently, he had developed insomnia. The leading psychopathological findings were distrustful contact behavior, psychomotor restlessness, narrowed formal thinking, persecutory delusion, depressed and anxious moods, and absence of any hallucinations or cognitive dysfunctioning. Further anamnesis revealed that psychotic symptoms were present for 10 days. Physical examination was unremarkable, and there was no history of mental disorder. The patient lived in a stable partnership and reported to be employed for 28 years in the same company as a technician. The patient had been treated successfully with oral roxithromycin 150 mg/d for 14 days until 2 days before admission. Otherwise, there was no history of somatic illness. The patient reported explicitly that he had never taken macrolides before. There was no other temporary or long-term medication.
During the detailed interview, it could be determined that paranoid symptoms began on day 7 of roxithromycin treatment. The patient admitted that he had been smoking marihuana on a daily basis for at least 35 years and had consumed cannabinoids as recently as the day before; he stated that he had consumed a stable dose of 1 to 2 g of marihuana per day during the last 20 years without significant dose variations. He plausibly denied the use of other illicit drugs, alcohol, and nicotine, in line with exclusive detection of THC in the qualitative urine drug screening. Blood tests were inconspicuous regarding differential blood count, thyroid function, liver and kidney function tests, and electrolytes. Because the patient refused an in-patient treatment with further diagnostic workup (examination of cerebrospinal fluid, electroencephalography, regular blood tests), tentative diagnoses of a cannabis-related psychotic disorder (Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition [DSM-5] 292.9), as well as cannabis use disorder (DSM-5 304.30), were made, and treatment with olanzapine 5 mg/d, outpatient follow-up treatment including a magnetic resonance imaging scan of the brain, and complete abstinence of cannabis were recommended. The patient was informed about the possible etiologic role of cannabis in regard to his psychotic disorder. Unfortunately, the patient refused a specific therapy for the substance use disorder and preferred to continue smoking marihuana. Because of the pronounced and predominant psychotic syndrome, the severity of the cannabis use disorder according to DSM-5 criteria could not be determined. On the next day, the patient presented again and demonstrated a remarkable improvement of psychotic symptoms after taking a single dose of olanzapine 5 mg; he reported to have continued the use of cannabis.