A case of tramadol-induced psychosis on a background of mixed substance use resulting in serious violence

To the Editor

We wish to describe the case of M, a 39-year-old man who was convicted of a serious offence following an act of uncharacteristically severe violence in the context of the rare but recognised phenomenon of tramadol-related psychosis (Chen et al., 2015).

M had limited psychiatric history prior to the onset of the psychosis. Two years prior to offending, he was prescribed escitalopram which he did not continue.

He had been a near daily user of cannabis from his teens but ceased his 2 g/day habit abruptly 1 month prior to the offence. He had been a daily user of alcohol throughout his adult life: up until approximately 1 month prior to his episode he had been drinking 6–12 bottles of beer, sometimes with spirits in addition, for some 12 months.

He had suffered with various orthopaedic problems for 16 years prior to the offence. Tramadol was initially prescribed 2 years prior.

A little over a year before the offence, M was forced to stop working, due to constant pain. His usage of tramadol subsequently escalated. By the time of the offence, he was prescribed tramadol SR 100 mg twice daily, and tramadol 50 mg one to two tablets PRN up to three times daily by his general practitioner (GP).

After ceasing his cannabis and alcohol, his pain worsened and his usage of tramadol escalated; he began taking more than the amounts prescribed: up to three 100 mg slow release tablets, and up to eight of the 50 mg immediate release tablets every day.

Based both on retrospective self-report and collateral reports from family, it appears that approximately 1 week prior to the offence, M abruptly developed a range of acute psychotic symptoms including

Delusions of reference that the television set was talking directly to him;

Persecutory delusions regarding his neighbours breaking into his house;

Grandiose delusions that he was a famous sportsman;

A Capgras-type delusion that one of his children had been replaced by an imposter.

In addition, he described a sense of ‘waking in and out of a dream all the time’.

Three days prior to the offending, M was reviewed by his GP but remained guarded regarding his psychotic symptoms. His GP diagnosed a depressive disorder and prescribed desvenlafaxine 50 mg daily. M took a higher dose than prescribed – 100 or 150 mg – hoping that a higher dose would ‘do something’ to help him recover more rapidly.

Following this, M suffered further deterioration in his mental state. He developed auditory hallucinations that he attributed to deceased relatives. He developed an intense persecutory delusional belief that his partner was poisoning the household, with associated transient visual hallucinations wherein he could see the poisonous substance. In this context, he carried out the offence, which was followed by a well-organised range of behaviours evidently intended to reduce the likelihood of criminal conviction.

Following arrest, M was assessed in hospital where acute neurological illness was excluded. There was no evidence of a ‘serotonin syndrome’. He was then transferred into custody, where his behaviour temporarily became more disorganised, with some mild disorientation to place, but within just over a week after arrest his symptoms had fully resolved, without antipsychotic medication being prescribed. There has been no recurrence.

Diagnostically, the possibility of a delirium could not be entirely excluded. However, there was an absence of amnesia, preserved capacity for organised behaviour and disorientation only became evident after incarceration. Conversely, psychotic symptoms, including hallucinations and a relatively organised delusional belief system, were prominent features. The preferred diagnosis was therefore ‘medication-induced psychotic disorder’ (ICD code F19.959).

The genesis of the psychotic disorder is likely to have been multifactorial. It is not possible to exclude the possibility that alcohol and cannabis withdrawal were of relevance. The timing of the onset of his disturbance, however, is somewhat later than would be expected if this were the predominant factor. His florid symptoms coincided with an escalation in his usage of the analgesic tramadol and we concluded that this was the predominant causal factor in his psychosis. His usage of desvenlafaxine at a higher dose than prescribed may have further aggravated his condition.

The mechanism for psychosis related to tramadol remains unclear; long-term exposure in rat studies revealed significant upregulation of dopamine D2 and D3 receptors in the nucleus accumbens upon repeated treatment with tramadol (Faron-Gorcka et al., 2004). There are also reports of serotonin norepinephrine reuptake inhibitor–related psychosis in the literature, possibly relating to its dopamine reuptake inhibiting action (Safeekh and Pinto, 2009).

Tramadol is a commonly used analgesic and prone to abuse. The Tramadol Consumer Medicine Information leaflet notes ‘confusion’ as a potential, although uncommon, side effect. Prescribing doctors need to be aware of the rare but recognised complication of acute psychosis, particularly when taken at doses in excess of the recommended range.