Abstract
Amphetamines have been extensively abused; tolerance, extreme psychological dependence and severe social disability may occur. Abrupt cessation following prolonged high doses can result in extreme fatigue and depression; changes are also noted on sleep EEG. The long-term use of dexamphetamine is associated with various adverse reactions including palpitations, tachycardia, hypertension, restlessness, dizziness, insomnia, headache, dyskinesia, tremor, exacerbation of tics, aggression, suicidal ideation and panic attacks. The stimulant effect is usually followed by depression, lethargy and exhaustion. The most severe manifestation of chronic intoxication is psychosis, often clinically indistinguishable from schizophrenia.
We report the case of a 68-year-old male who presented with over 25 years use of high-dose dexamphetamine prescribed for narcolepsy. The man had a history of alcohol dependence over 40 years, chronic depression and anxiety on a background of an anxious/dependent personality disorder.
The current admission was precipitated by the death of a family member with dementia, relapse of alcohol abuse, worsening anxiety and depression. On review, the patient had previous diagnoses of narcolepsy, epilepsy, possible Huntington's disease (the case notes documented caudate atrophy), dementia, schizophrenia, Parkinson's disease, alcohol dependence, anxiety and depression with suicidal ideation, previous head injuries, hypertension, hypercholesterolaemia and hepatic cirrhosis. He was on the following medications: dexamphetamine 15 mg, sodium valproate 1g bd, mirtazapine 60 mg, fluoxetine 40 mg, irbesartan 150 mg, omeprazole, thiamine and atorvastatin.
Physical examination revealed hypertension, choreoathethoid movements suggestive of tardive dyskinsia, pill rolling involuntary movements in both hands (right greater than left) and oro-facio-mandibular movements. The abnormal involuntary movement score (AIMS) was 52. Liver function tests (LFTs) were abnormal; GGT 541 U/L (0–50), ALT 192 U/L (<45), AST 193 U/L (<45). B12, folate and thyroid were normal. Mental state examination revealed features of anxiety and depression, and thought content included existential issues about developing dementia and dying in a nursing home.
At this stage, it was difficult to differentiate iatrogenic (medication induced) manifestations from true mental illness and we sought to do more investigations. MRI showed moderate generalized cortical atrophy with no caudate atrophy, EEG and Huntington's disease screen were normal. There was no evidence to suggest that he had schizophrenia, narcolepsy or cirrhosis (as LFTs reverted to normal). However, some previous seizure activity correlated with alcohol withdrawal. His clinical and neuropsychological assessments were not conclusive of dementia.
The patient volunteered for a medication-free trial. The above medications were weaned over a 4-week period, with dexamphetamine as the final drug (apart from thiamine and atorvastatin). However, the patient received low-dose quetiapine in the interim to manage anxiety. We monitored for any deterioration.
The patient was discharged after receiving psychological intervention such as psycho-education, grief therapy, addressing existential issues and relapse prevention strategies to address alcohol-related issues and the potential of future developing dementia. He responded to a trial of amitryptiline, though he had residual symptoms as measured by the Hamilton Depression Rating Scale (baseline 20, discharge score 10) and the Hamilton Anxiety Rating Scale (baseline 18, discharge score 13). These residual symptoms could perhaps be explained by his cluster C personality, effect of dexamphetamine discontinuation and treatment refractory depression and anxiety.
Focusing on dexamphetamine abuse, the patient presented with symptoms of anxiety, depression, craving, physiological dependence, physical symptoms such as involuntary movements, high blood pressure, tachycardia, and autonomic instability. He developed some features of dexamphetamine discontinuation with increased craving, insomnia, irritability, low motivation and subjective worsening of depression and anxiety following cessation of the offending agent. His involuntary movements improved markedly, with reduction in AIMS to less than 10 from a baseline of 52 after 6 weeks. His blood pressure stabilized without the need for antihypertensive agents.
This case report illustrates the effects of dexamphetamine abuse in an elderly man. Reversal of the various physical and psychological symptoms occurred following cessation of dexamphetamine. We wonder, given the positive family history of dementia and longstanding alcohol abuse, whether the long-term effect of dexamphetamine abuse could contribute towards the development of future subcortical dementia and propose that further research investigate that possibility.