Management of Refractory Catatonia Associated With OCD Exacerbation in a Patient With Bipolar I Disorder: A Case Report

A 31-year-old with Bipolar I Disorder (BD-I) and longstanding comorbid obsessive-compulsive disorder (OCD) was re-hospitalized for severe exacerbation of OCD symptoms associated with intolerable distress and inability to cope at home. This occurred one week after discharge for a recent manic episode with mixed and catatonic features. The recent hospitalization involved six sessions of bilateral electroconvulsive therapy (ECT) and a switch from olanzapine to loxapine as part of his triple anti-manic therapy with ongoing lithium and valproate.

Since his mania onset in his early twenties, the course of illness was characterized by four manias, two depressions, and one mixed state with unspecified polarity. One of his four manic episodes was medication-induced, following the use of an antidepressant for depressive symptoms. There were eight psychiatric admissions and three episodes of catatonia associated with depression or mania. One of these involved developing bilateral pulmonary emboli as a complication of his catatonia.

At the time of admission, he did not initially present with any depressive, (hypo)manic or catatonic symptoms, and his lithium and valproic acid levels were within therapeutic ranges. Within week one in the hospital, emerging signs of catatonia and/or “obsessive slowness” appeared, including marked psychomotor retardation, speech abnormalities ranging from mutism to one-word responses or halting speech, ambitendency, and intermittent thought blocking, with a frequently fluctuating pattern. Intense preoccupation with his predominantly mental rituals and obsessions resulted in difficulty with self-initiating behavioral responses. By week three, he developed acute stuporous catatonia, which included immobility, mutism, catalepsy, waxy flexibility, grimacing, and negativism. An intramuscular lorazepam challenge elicited a partial response within 30 min of administration, so oral lorazepam 2 mg three times daily was initiated. Medical work-up was non-contributory.

Due to prior ECT response and residual catatonic symptoms despite high-dose benzodiazepines, five sessions of bilateral ECT were administered and tolerated well, but only to partial effect (Bush-Francis Catatonia Rating scale score = 12/69). As such, clomipramine was introduced along with ongoing ECT despite concerns about manic induction (especially given the recent manic episode) and gradually uptitrated to 50 mg daily. After notable and sustained improvement in his OCD and catatonia, ECT was stopped after 11 sessions. The patient remained stable and was discharged home.

Two days following discharge, the patient was readmitted to hospital with acute re-worsening of OCD and manic symptoms. He had missed one dose of loxapine due to a prescription error. The manic symptoms rapidly resolved upon readmission; however, he again presented with intermittent catatonia that resolved with oral lorazepam. Clomipramine was increased to 75 mg daily for a 3-day period but reverted to 50 mg at discharge due to emergent hypomanic symptoms and potential worsening of catatonia. Quetiapine 200 mg replaced loxapine to address both OCD treatment and mood stabilization. Ultimately, the patient was again discharged home despite residual, suboptimally treated OCD per strong patient preference for outpatient management after three protracted back-to-back admissions.

Patients with BD have an estimated 10%–20% lifetime co-prevalence of OCD. The tension between mood stabilization and potential affective switch from antidepressant pharmacotherapy for comorbid obsessive-compulsive and related disorders is well documented.

In our case, the emergence of OCD-related catatonia complicated the treatment planning by adding another treatment target and necessitating a more rapid approach. Catatonia can present as a primary OCD manifestation in the absence of psychotic or mood symptoms, although this is likely uncommon, with only a handful of case reports published to date depicting this presentation [1]. Although it remains unclear how the pathophysiological processes underlying catatonia and OCD converge, especially within the context of BD, it is posited that serotonin hypofunction found in all three disorders may result in shared vulnerability. The difficulty of diagnosing catatonia generally and in the setting of OCD due to overlapping features may result in the underappreciation of this clinical state.

The first-line treatment of catatonia consists of high-dose benzodiazepines, followed by electroconvulsive therapy. The divergence in treatment protocol begins to occur, however, when patients do not respond to this treatment sequence. Refractory catatonia comprises approximately 15%–30% of cases, where treatment approaches are influenced by suspected etiology.

In the context of BD, there is a very sparse evidentiary base to guide clinicians to treat catatonia. In the absence of any clinical guidelines and based on limited case-report literature, second-line pharmacotherapies for catatonia occurring in BD include atypical antipsychotics, glutamate antagonists, and anticonvulsants. There is some evidence that the latter, namely valproic acid and carbamazepine, may be particularly effective in the context of an underlying manic state while providing additional mood stabilization [2].

In OCD, although selective serotonin reuptake inhibitors (SSRIs) are well-established as first-line pharmacotherapy, clomipramine was identified as a potential option with a particularly unique advantage in our context. Clinical experience drawn from a large OCD specialty clinic within our institution suggested that improvement of OCD symptoms was not uncommonly achieved with doses of clomipramine below 100 mg daily, and as low as 30 mg daily. This clinical impression is supported pharmacodynamically by a study of healthy volunteers which identified that a single 10 mg dose of clomipramine resulted in approximately 80% serotonin transporter occupancy, the putative threshold necessary to obtain therapeutic effect [3]. In contrast, the target therapeutic dose ranges for SSRIs and SNRIs in OCD exceed antidepressant dosing, therefore taking longer to titrate and potentially increasing switch risk. At a final clomipramine dose of 50 mg, it would be anticipated that the serotonin transporter occupancy would be well over 90% [3].

Although tricyclic antidepressants are largely avoided in BD patients due to a higher switch risk, this caution relies on clinical studies that were conducted using desipramine. With a binding profile very distinct from desipramine, the known high specificity of clomipramine for serotonergic targets with minimal effects on noradrenergic neurotransmission means its theoretical risk of affective switching is likely comparable to that of SSRIs with similar pharmacodynamic profiles. Clinicians must nevertheless ensure optimal co-treatment with mood stabilizers among BD patients to buffer against switch risk, as developed with our patient (Figure 1).

Second-generation antipsychotics (SGAs) were initially excluded from consideration due to the patient's history of putatively worsening OCD symptoms on olanzapine in previous admissions. Some authors have asserted that the use of antipsychotics should be generally discouraged or exercised with great caution, as antipsychotics, especially high potency typicals, can cause or worsen catatonic symptoms and precipitate malignant catatonia [4]. This is contrasted by a large number of case reports where SGAs have been successfully used for treatment-refractory catatonia, including catatonia secondary to OCD in several instances. A recent RCT for OCD with co-morbid BD in its euthymic phase found quetiapine to be an effective adjunct [5]. Outside of the BD context, the augmentation of standard serotonergic medications with atypical antipsychotics is one of the most robust evidence-based strategies for treatment-resistant OCD. Quetiapine specifically has level 2 evidence. The evidence supporting the role of glutamate modulators, such as topiramate and memantine, as therapeutic augmentation for OCD-BD is growing, but the trials to date studied OCD symptoms in the manic phase.

The second admission during which clomipramine 75 mg was associated with an affective switch led to initiating quetiapine due to the added anti-manic effects. By the time of discharge, his catatonic and OCD symptoms were controlled sufficiently such that the patient could safely leave the hospital in a euthymic state.

Catatonia generates another layer of diagnostic and therapeutic challenges to the already high complexity of the intersection between OCD and BD. The limited and conflicting body of evidence available to guide decision-making beyond the first-line interventions makes it challenging to navigate the clinical dilemmas. This report also highlights the significant gap in research but some clinical considerations on the treatment aspects of this highly prevalent OCD-BD comorbidity.