A case of delirious mania in the context of concurrent cardiac comorbidities and autonomic instability

A 26-year-old male with schizoaffective disorder and hypertrophic obstructive cardiomyopathy presented with delirious mania. His 23-week hospitalization involved managing severe mood and psychotic symptoms with fluctuating responses to medications, highlighting the complexities of treating delirious mania in patients with significant cardiac risks. A 26 year old male presented to the psychiatric emergency department after reportedly having dialed 911 himself stating his "water broke" and that he is having his period. He presented with multiple grandiose delusions, including that he was a multiple PhD candidate and his university was making him Provost. Urine toxicology screen was negative for substances. The patient's lithium level was 0.6 meq/L (therapeutic range 0.8–1.2 meq/L); he reported recently skipping several doses of lithium. On evaluation, the patient was reclining at the edge of the bed, scrub pants lifted and staring at his genitals. The patient was speaking fast, illogically, and tangentially with thought blocking. He endorsed visual hallucinations of the virus that he reported in his genitals, "a blue virus, walking around!" and auditory hallucinations non-command in nature. He appeared internally preoccupied and denied passive or active suicidal or homicidal ideation, plan, or intent. The patient's medical history was notable for hypertrophic obstructive cardiomyopathy (HOCM) with Wolff-Parkinson-White syndrome, sickle cell trait, chronic thrombocytopenia, acne keloidalis nuchae of the scalp, and hypertension. The patient has a history of treatment-resistant schizoaffective disorder, bipolar type, with intermittent catatonic tendencies. Diagnosed at age 22, the patient had multiple extended psychiatric hospitalizations totaling 6 months in the first year after diagnosis. He then remained stable and pursued a graduate degree for about 2 years. However, 13 weeks of hospitalization for suicidal ideation and an acute exacerbation of schizoaffective disorder preceded the current case. A 2 mg lorazepam challenge during that hospitalization was negative. This previous hospitalization ended 4 weeks before the current one. The patient was subsequently hospitalized for 23 weeks with a rapidly fluctuating psychiatric clinical course complicated by various medical issues, for which he was transferred between the medical floors and the psychiatric unit. Notably, the patient had periods of autonomic instability that seemed to correlate with exacerbations of his psychotic and mood symptoms, as shown in Figure 1. The patient's mood and psychotic symptoms had extreme ranges in presentation during his hospitalization. At times the patient would present with symptoms of catatonia (posturing, mannerisms, verbigeration, waxy flexibility, excitement, combativeness) that would gradually dissipate over a period of days with treatment, followed by periods of more aggressive presentations that would include verbal threats, disinhibition, and psychomotor agitation. The patient would also have manic symptoms including pressured rapid speech, flight of ideas, euphoric affect, and decreased need for sleep with shifting (at times bizarre) delusions, at one time reporting he was writing equations that were the "autograph of God." Another extreme presentation was episodes in which he described a depressed mood with multiple references to his mother's early death and feelings of loss, sometimes reporting hearing the voices of the dead. Given the patient's seemingly constant shift in symptomatic presentation, his medication regimen was adjusted accordingly. Generally, the patient's regimen consisted of a mood stabilizer, a benzodiazepine, and an antipsychotic. The patient was continued on lithium 300 mg by mouth (PO) twice a day (BID) dose from his previous hospitalization and titrated up with little effect, leading to the addition of oxcarbazepine 150 mg PO BID and relative stability for 2 weeks (prescribing valproic acid in lieu of oxcarbazepine was considered, though it was ultimately decided against due to bleeding risk). Lithium was discontinued when the patient developed acute kidney injury (Figure 1, letter b) and experienced severe psychiatric decompensation. Oxcarbazepine was discontinued when the patient developed leukopenia on week 11 (Figure 1, letter c). The patient was then relatively stable without a mood stabilizer until week 15, when he again deteriorated with prominent mania and psychosis with concurrent rhabdomyolysis. Lithium was restarted with the rationale that it may be more effective after time off the medication and was titrated up to Lithium 600 mg PO BID by discharge. In terms of benzodiazepines, the patient was initially started on clonazepam 0.5 mg PO BID from his previous hospitalization and was increased to 1.5 mg PO three times a day (TID) due to increased aggression. The dose was again decreased to 1 mg PO in the morning (QAM) and 2.5 mg PO at night (QHS) the following week due to concern for oversedation and depressive symptoms. The patient's symptoms stabilized at this point and clonazepam was tapered off during week 6 due to clinical improvement. However, the patient psychiatrically decompensated without any further medication changes. At this point delirious mania was more strongly considered, in part due to the patient's psychiatric decompensation after no other changes besides tapering of clonazepam as previously described. Because of this, he was initially switched to lorazepam 2 mg PO QAM and 3 mg PO QHS, as this is the most widely studied agent in the treatment of delirious mania. He was again switched back to an equivalent dose of clonazepam. During week 15, the patient deteriorated into overt mania and psychosis once again with concurrent rhabdomyolysis, an upper respiratory infection, and high anion gap metabolic acidosis and was titrated up to lorazepam 4 mg PO TID (with no apparent signs of over-sedation) again targeting symptoms noted to be consistent with described cases of delirious mania. His manic and psychotic symptoms improved and resolved, lorazepam was tapered down to 1 mg PO QAM and 1 mg PO QHS over the course of several weeks until discharge. The patient was initially started on paliperidone 3 mg PO QD and was increased to 12 mg PO once a day for worsening psychosis. However, due to fever with inability to rule out the possibility of malignant catatonia, paliperidone was decreased to 6 mg PO QD on week 7 with resolution of symptoms, unclear of relation to the dose change in antipsychotic, as fever did not return, and no other symptoms of catatonia were noted. The patient remained stable until week 15, when multiple medical issues (including head trauma, rhabdomyolysis, suspected influenza A infection) and severe psychiatric decompensation led to a decision to cross-titrate paliperidone with olanzapine. Olanzapine was titrated up to 22.5 mg PO QHS prior to discharge. This case highlights the challenges in the treatment of delirious mania in the context of comorbid cardiac comorbidity. As stated previously, the patient was relatively stable for 2 years from the age of 23 to 25 on an unchanged medication regimen that the patient reported adherence to. There is some diagnostic uncertainty in terms of malignant versus non-malignant delirious mania, as the patient's autonomic instability (mostly consisting of bradycardia, three episodes of fevers with unclear origin, and fluctuating blood pressures) may be related to his HOCM.1 If his autonomic instability is attributed to his cardiac abnormalities, the patient would better fit the picture of non-malignant delirious mania with catatonia. Therefore, the patient's positive response to a combination of antipsychotic, mood stabilizer, and benzodiazepine would support a proposed treatment algorithm by Spiegel et al.2 Although Electroconvulsive therapy (ECT) is a proposed treatment option for delirious mania,3 this was ultimately not viable due to lack of availability at the facility the patient was admitted to, coupled with the patient lacking capacity to accept ECT and his next of kin deciding against ECT as a possible intervention. Ultimately, the question that emerged through the course of the patient's clinical treatment was the risk versus benefit analysis of using higher doses of medications or adding agents in the context of concurrent HOCM and intermittent bradycardia. With the patient's refusal to obtain an implantable cardioverter defibrillator, the patient's cardiology team indicated that there is about a 30% chance of death in the next 5 years. As almost all commonly used psychiatric medications will increase risk of arrhythmia,4 it is impossible to predict how much each medication at each dose will increase the patient's chance of death or if the documented risk will have a more pronounced effect given the patient's existing cardiac abnormalities. The limited availability of quantitative information in this regard makes decision making regarding dose changes or switching medications challenging. Despite the severity of the patient's cardiac conditions, the acute risks posed by untreated psychiatric symptoms, including constant motor activity, aggression, and lack of sleep, necessitated psychotropic treatment despite their risks. In addition, the patient's aggressive behavior would at times put him in harm's way, resulting in acute physical injury due to conflict with other patients. These episodes of agitation would also require urgent intramuscular administration, increasing medication burden along with cardiac risk. Moreover, the patient's history of prolonged hospital stays indicates that without proper psychiatric treatment, the patient would likely constantly be a danger to himself and others and require involuntary admission. Finally, the shared decision making with the patient required in these complicated scenarios was impossible during the patient's steep alterations in consciousness while his psychiatric illness was uncontrolled. More research is needed in the treatment of patients with significant cardiac risk factors in the setting of delirious mania. In examining overall patient care in this case, a nuanced risk benefit analysis is required to balance the patient's cardiac risk with treatment of his underlying psychiatric presentation. The authors would like to acknowledge the patient that the following case report is based on, who agreed to allow the team to share his clinical presentation and treatment. The authors declare that they have no conflict of interest. Written informed consent was obtained from the patient to write about and publish his clinical case. The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.