Lithium and tricyclic antidepressant-induced delirium presenting with prominent dyspraxia: case report

Introduction

Long-term treatment with lithium has been associated with mild cognitive impairment, mental slowing and memory impairment [Cookson, 1997]. Neurological complications such as muscle weakness, drowsiness, ataxia, confusion and dysarthria can be late signs of lithium toxicity [Tyrer, 1996], but idiosyncratic cases have also been reported [McGovern, 1983; Brown and Rosen, 1992]. In one such case, McGovern described an elderly female patient, with a history of endogenous depression, who developed tremor, vertigo, ataxia and dysphasia, following the initiation of lithium within normal therapeutic serum levels [McGovern, 1983]. In addition, Brown and colleagues described the case of a 64-year-old woman with a 25-year history of schizoaffective disorder who developed delirium following treatment with lithium, also within the therapeutic serum level [Brown and Rosen, 1992].

Tricyclic antidepressants can also cause neurological side effects such as confusion, impaired memory and paresthesia [Joint Formulary Committee, 2011]. Although, there are no case reports of dyspraxia associated with tricyclic antidepressants when used alone in the literature.

However, there is an increased risk of toxicity when tricyclic antidepressants are used in combination with lithium. Worrall and colleagues published a case describing slowly developing constructional dyspraxia and mild dysphasia in a 50-year-old female patient with a 2-year history of endogenous depression [Worrall and Gillham, 1983]. After responding to a combination of lithium and amitriptyline for 14 months, she began to complain of difficulties in finding words in conversation and of memory impairment. These problems resolved completely when the lithium was stopped and amitriptyline continued.

In our report, we describe a case of delirium presenting with prominent dyspraxia at therapeutic lithium serum levels, following several years of uneventful lithium administration, but within 3 months of the addition of clomipramine. The case described above [Worrall and Gillham, 1983] improved when lithium was stopped but this presentation resolved when clomipramine was withdrawn. This suggests that an idiosyncratic interaction between tricyclic antidepressants and lithium can cause delirium with dyspraxia.

Case report

A 57-year-old retired lorry driver was regularly reviewed because of bipolar affective disorder and obsessive–compulsive disorder (predominantly obsessional thoughts or ruminations). He had several cardiovascular risk factors including non-insulin-dependent diabetes, hypertension and hypercholesterolemia. Clomipramine was titrated up to 150 mg nocte in addition to long-standing lithium carbonate (Priadel®) 800 mg nocte and quetiapine 500 mg nocte. There were no neurological or gastrointestinal signs of lithium toxicity but mild memory problems emerged a few months thereafter (MMSE 27/30). Clomipramine and quetiapine doses were reduced to 50 mg nocte and 300 mg nocte respectively to address any anticholinergic side effects but the patient required admission for assessment of an apparent dementing illness 4 months later. Dyspraxia was the presenting complaint but the deterioration was delirious in nature with nocturnal worsening, visual misinterpretations and disorientation. The patient could not orientate clothing or understand previously routine implements such as TV remote control and car electronic key fob. CT brain was unremarkable but MRI could not be tolerated because of claustrophobia. NM Brain HMPAO (Ceretec) scan suggested ‘ill-defined defects of tracer uptake scattered throughout both cerebral hemispheres, particularly in the periventricular regions’ as is consistent with cerebrovascular disease (these findings are not considered abnormal in a man of this age with diabetes and neither the radiologist’s report or the Addenbrooke’s Cognitive Examination on recovery suggested that the scan was significant). Addenbrooke’s Cognitive Examination scored 67/100 (attentional and orientation 15/18, memory 12/26, fluency 9/14, language 23/26, visuospatial 8/16). The patient tried, but could not draw the overlapping pentagons, wire cube or clock face components of this cognitive examination. Serum lithium level was 0.44 mmol/l (therapeutic range 0.4–1.0 mmol/l).

In light of a case report on lithium and amitriptyline (tricyclic antidepressant) causing constructional dyspraxia [Worrall and Gillham, 1983], the clomipramine (tricyclic antidepressant) was gradually withdrawn. One month later, the patient said he ‘was back to his usual self’ with Addenbrooke’s Cognitive Examination 90/100 (scattered deficits, visuospatial 14/16). One year later, the presentation and Addenbrooke’s Cognitive Examination score remain stable.

Comment

This report describes delirium with prominent dyspraxia occurring at low-therapeutic serum lithium levels on the coprescription of clomipramine. This could have been a delirious side effect of clomipramine in a susceptible individual but the severity of the dyspraxia was unusual. The cognitive impairments resolved when clomipramine was stopped but lithium continued. A report describing constructional dyspraxia on lithium and amitriptyline incriminated the lithium but acknowledged that the tricyclic antidepressant and lithium combination could have been causal [Worrall and Gillham, 1983]. Hence, in addition to the recognized long-term cognitive effects of lithium and reports of acute confusional states emerging in patients previously established on lithium [Niethammer et al. 2000], this report suggests that a confusional state with prominent dyspraxia could be associated with the combined use of tricyclic antidepressants and lithium.