Abstract
A withdrawal syndrome following abrupt or gradual cessation of heterocyclic antidepressants has been well documented [1,2]. Common symptoms are nausea, emesis, anorexia, diarrhea, rhinorrhea, diaphoresis, myalgias, paresthesias, anxiety, agitation, restlessness and insomnia [1]. However, delirium has only rarely been described as a symptom of tricyclic antidepressant withdrawal [3]. The World Health Organization reports on the global burden of disease projects that depression will become the second leading cause contributing to disease burden worldwide by 2020 [4]. Although the total market share of tricyclic antidepressants has fallen to 12.8%, two tricyclic antidepressants feature in the top ten best selling antidepressants in Australia. Dothiepin figures at number eight on this list. Despite the marked fall in popularity, significant amounts of tricyclic antidepressants continue to be prescribed in actual clinical practice [5]. The discussion of this case comes as a timely reminder of the complexities of antidepressant withdrawal, especially where tricyclic antidepressants are involved and at a time when psychiatrists are becoming increasingly unfamiliar with the use of the older antidepressants.
Mr JD is a 94-year-old man with a long history of depression who had been doing well on prophylaxis with a 175 mg of Dothiepin. He was admitted to hospital in the context of a recent onset of frequent falls and was found to be dehydrated with a urinary tract infection. At admission there was no evidence of delirium. The urinary tract infection was treated with antibiotics with good result. He was found to have postural hypotension that was attributed to the dothiepin despite other possible pharmacological culprits: diuretic antihypertensive agents. The dothiepin was ceased abruptly precipitating deterioration in his affect and an associated delirium in the ensuing 72 hours. There was no laboratory evidence of other etiological causes that might explain a delirium. Working on the premise of a dothiepin withdrawal-related delirium he was represcribed dothiepin with a swift resolution of his delirium.
Agitation and brief perceptual abnormalities are acknowledged symptoms with tricyclic antidepressant withdrawal. Mr D however presented with the full complement of symptoms that would satisfy DSM-IV criteria for a diagnosis of delirium over a 4-day period suggesting that perceptual abnormalities were far more serious than the fleeting events that have been described so far in literature. The symptoms included disorientation in time and place, sundowning, agitation, confusion and difficulties with working memory. The exact cause of withdrawal-induced delirium is still unclear. It has been hypothesized that antidepressant-induced supersensitivity of central and peripheral muscarinic cholinergic mechanisms may account for commonly observed antidepressant withdrawal phenomena [6,7]. Similar cholinergic mechanisms may well be implicated in the genesis of this patient's delirium.
Most psychiatrists in consultation liaison practice would advise the cessation of cholinergic agents such as dothiepin or amitryptiline in a client suffering from delirium. However, if the delirium were to inexplicably recur or worsen one should suspect withdrawal-associated delirium and reinstate treatment with the respective tricyclic in favour of a more gradual withdrawal or alternatives such as dosage reduction rather than cessation.