# 24 - 7. Psychiatric effects of non psychiatric dru

# 7. Psychiatric effects of non-psychiatric drugs

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High-potency benzodiazepines such as triazolam can cause anterograde amnesia. 
Paradoxical disinhibition is seen in a few patients especially when preexisting brain damage is 
present. Triazolam is banned in UK since 1991 following reports of disinhibition and aggression. 
Benzodiazepines can produce respiratory impairment especially in those with COPD or sleep 
apnea. Benzodiazepines are better avoided in those with myasthenia gravis, head injury or 
porphyria due to this risk. 
Alprazolam can cause weight gain via appetite stimulation. 
Cleft palate and lips are teratogenic effects associated with benzodiazepines; withdrawal 
syndrome is seen in a neonate with third trimester use. 
Z-hypnotics have more potential to cause upset stomach and diarrhea compared with 
benzodiazepines. 
Eszopiclone’s  unique  temporary  side  effect  is  an  unpleasant taste. It can also cause dry mouth 
especially in the elderly in a dose-dependent fashion. 
The occurrence of benzodiazepine withdrawal syndrome depends on 
 The duration of treatment, 
 The dosage prescribed, 
 The rate of tapering and 
 The half-life of the compound. 
Benzodiazepine withdrawal is characterized by anxiety, diaphoresis, kinaesthetic hallucinations, 
restlessness, irritability, light-headedness, tremor, insomnia, autonomic hyperactivity, and 
weakness. In severe cases, depression, paranoia, delirium, and grand mal seizures are seen. The 
syndrome can occur after 1 or 2 weeks in long-acting benzodiazepines. Alprazolam and 
lorazepam are associated with immediate and severe withdrawal syndrome and should be 
tapered gradually. 
Using prescribed benzodiazepines for 4 weeks or less rarely results in significant withdrawal 
symptoms. But if used for 4 months – 5-10% have withdrawals; in 2 years – 25-45% and in 68years – 75% develop withdrawal syndrome and dependence pattern (Law et al. 2004). 
Slow taper at a rate of 25% per week, use of longer acting agents when tapering, avoiding longterm use of short-acting benzodiazepines, use of carbamazepine to assist discontinuation are the 
various strategies employed to manage withdrawal symptoms. 
7. Psychiatric effects of non-psychiatric drugs

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Non-psychiatric drugs 
Psychiatric side effects 
Beta-blockers 
Sedation, nightmares, dysphoria (nearly 50% in some samples) and depression. 
Psychiatric effects are seen only with lipophilic compounds e.g. metoprolol and 
propranolol. 
Angiotensinconverting enzyme 
(ACE) inhibitors 
Increased arousal, anxiety, fatigue, insomnia and increased psychomotor 
activity (4-8%) 
Clonidine 
Sedation or lethargy (35%); anxiety (3%), agitation (3%), depression (1%), and 
insomnia (1%). 
Nitrates/nitrites 
Delirium, psychosis (including delusions), anxiety, restlessness, agitation, and 
hypomania. 
Digoxin 
Depression and delirium (even in therapeutic levels) 
Statins 
Uncertain association with depression (evidence inconclusive) 
Corticosteroids 
Mood changes (mania more than depression), anxiety, agitation, lethargy. 
Dose-dependent. 1 in 6 patients has psychiatric side effects if prednisolone is 
prescribed in doses above 80mg/day. Symptoms start within 2 weeks. More 
common in females and those with past psychiatric history. 
Anabolic androgenic 
steroids 
 
Acute paranoia, delirium, mania or hypomania, homicidal rage, aggression, 
and extreme mood swings, as well as a marked increase in libido, irritability, 
agitation, and anger. Usually dose-dependent and resolve in 1-4 weeks after 
stopping the steroids. 
Gonadotropinreleasing hormone 
(GnRH) agonists (e.g. 
leuprolide) 
Depressive symptoms 
Interferon-alpha 
Nearly 40% develop psychiatric side effects; ~20% experience depression. Seen 
in first 12 weeks of treatment. 
Penicillin 
Sedation, anxiety and hallucinations 
Cephalosporins 
Delirium 
Ciprofloxacin and 
ofloxacin 
Restlessness, irritability, lethargy, tremors, insomnia, mania, depression, 
psychosis,  delirium,  seizures,  or  catatonia  (incidence  ≤1%) 
Isoniazid 
Delirium, mania, depression, and psychosis. 
Tetracyclines 
Depression, insomnia, and irritability at high dosages. 
Antihistamines and 
Atropine-like psychosis

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decongestants 
Proton pump 
inhibitors & H2antagonists used for 
peptic ulcer disease 
Confusion, agitation, depression, and hallucinations— mainly in geriatric 
patients with impaired hepatic-renal function. 
 
Ondansetron 
Anxiety 
Isotretinoin 
Severe depression and suicidal behavior. 
Aminophylline and 
salbutamol 
Agitation, insomnia, euphoria, and delirium 
 
Depressogenic drugs 
x Beta blockers 
x Calcium channel blockers 
x Interferons (alpha > beta) 
x Steroids 
x Cyproterone, progesterone 
x Varenicline 
x Isotretinoin 
x Ezetimibe 
 Rimonabant: Two endocannabinoid receptors CB1 and CB2 are identified; based on the clinical 
observations of cannabis related increase in appetite  (the  “munchies”), researchers have studied 
the involvement of endocannabinoid system in the control of energy balance. Rimonabant, the 
first  of  the  CB1-receptor antagonists, was developed as an anti-obesity agent on the premise that 
blocking central cannabinoid activity might reduce food intake. But there is compelling evidence 
that rimonabant is associated with the development of severe adverse psychiatric events (2.5 
times more depression; suicidal ideas and 3 times more anxiety). 
Animal studies have consistently shown that pharmacological blockade of the CB1 receptor 
impaired the anti depressant-reducing or anxiety-reducing actions of endocannabinoids. FDA 
has issued a warning now on the use of this agent.