Antipsychotic-induced urinary dysfunction: anticholinergic effect or otherwise?

Abstract

Although urinary difficulties such as incontinence (UI) and retention (UR), reported with both typical and atypical antipsychotics, have been hypothesised as being a form of extrapyramidal side effects or due to anticholinergic side effects, we believe this may not be the case. We report here a male patient with bipolar disorder who developed urinary difficulties with antipsychotics, both typical and atypical, and in whom only aripiprazole seemed to work. We also hypothesise on the possible mechanisms of adverse urinary effects of antipsychotics.

BACKGROUND

Urinary difficulties such as incontinence (UI) and retention (UR) which can impact patient compliance are rare adverse effects of antipsychotic agents. UI has a reported prevalence of 3–6 %¹ and has been described with nearly all typical antipsychotics,² in various dosages² and without pre-existing bladder dysfunction or urinary problems,¹ but has been very rarely reported with atypical antipsychotics.^3,4 UR, on the other hand, has been reported even more rarely.⁵ Previously, these urinary difficulties have been described as being a form of extrapyramidal side effects¹ or due to anticholinergic side effects.⁶ We, however, believe that this may not be the case. Initially, we had reported a young male patient with bipolar disorder who had developed urinary difficulties with antipsychotics, both typical and atypical, and in whom only aripiprazole seemed to work.⁷ Here we report another patient, a middle-aged male, who developed similar problems and responded to aripirazole. We also hypothesise on the possible mechanisms of urinary adverse effects of antipsychotics.

CASE PRESENTATION

Our patient, a 38-year-old drug-free male, was admitted to our tertiary care psychiatric institute with a second episode of bipolar I mania (DSM IV TR), with no contributory family history, a past history of a manic episode treated at our hospital and a normal physical examination. He developed acute UR with injectable haloperidol 10 mg/day for which he had to be catheterised. Haloperidol was stopped and th epatient recovered from his urinary difficulties in 2 days. Case history review revealed that the patient had developed marked urinary difficulties with UI, a complaint that he had never had before, on treatment with various antipsychotics including oral haloperidol (10 mg/day), olanzapine (10 mg/day) and risperidone (4 mg/day) also during his previous admission, which had led him to discontinue treatment. However, he had no other side effects including extrapyramidal syndrome (EPS). Based on his chart review, aripiprazole 5 mg was started and later increased to 15 mg, and the patient was closely observed for development of any side effects such as UR.

INVESTIGATIONS

Routine investigations in the current admission including renal function tests, urine culture and abdominal ultrasonography were within normal limits.

OUTCOME AND FOLLOW-UP

The patient remained asymptomatic until discharge from hospital and on follow-up after 1 year.

DISCUSSION

We believe that as female gender, older age, prior urinary or bladder problems, treatment with typical antipsychotics and development of EPS appear to be positive risk factors,^1,8–11 our patient, being of middle age, male and lacking any family history, presented a low to moderate risk. Being uniquely susceptible to both typical and atypical antipsychotics from the first day of treatment, and developing both UI and UR without development of EPS are the real factors to be noted in this patient. Further, the lack of any adverse urinary effect with aripiprazole is worth noting. The combination of UI and UR in this patient also suggests the possibility of a genetic predisposition,¹² which however needs to be investigated further and which will be helpful in predicting an individual patient’s drug response.¹³ It may also be possible that the different formulations of haloperidol used in both treatment periods (oral vs injectable) may be responsible for the differing reactions (UI vs UR) since injectable haloperidol would be expected to act rapidly and possibly cause adverse effects early, when compared with the oral form. In the meantime, one also cannot rule out any idiosyncratic vulnerability which has rendered our patient susceptible to both UR and UI.

Further, since α1-adrenergic receptors are widely distibuted over the lower urinary tract, especially over the smooth muscle of the trigone and detrusor muscle of the bladder, and promote urinary continence,¹⁴ we believe that central dopamino-sertoninergic effects along with peripheral α1-adrenergic blockade may act synergistically to cause UI and/or UR.^15,16 The fact that all the antipsychotics—haloperidol, olanzapine and risperidone—which have considerable central dopaminergic blockade and agonist action on α1-adrenergic receptors¹⁶ caused UI/UR in this patient, while aripiprazole, which has minimal effects on α1-adrenergic receptors and only a partial antagonist action at central D2 receptors,¹⁷ did not cause urinary symptoms, further bolsters this argument. This unique mechanism of action may explain the lack of adverse urinary effects with aripiprazole in this patient, suggesting that it may be tried in patients with a history of urinary complaints and the mentally ill elderly who have a propensity to develop urinary symptoms. Although an earlier report had commented on urinary obstruction with aripiprazole,¹⁸ we believe that this action was due more to citalopram than to aripiprazole alone, and hence aripiprazole can be seriously considered as an alternative to conventional antipsychotics in the elderly.

LEARNING POINTS

• Antipsychotic-induced urinary dysfunction may not be due to their anticholinergic effects; instead the action may be more on peripheral adrenergic action.

• Pharmacogenomics may dictate the development of certain adverse effects of drugs.

• Aripiprazole does not cause urinary dysfunction and may be tried in the elderly, who are more prone to develop this adverse effect.