Evidence-Based Reviews

Watch for nonpsychotropics causing psychiatric side effects

Current Psychiatry. 2008 April;7(4):61-74

References

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Reflux medications. Two primary classes of reflux medications are proton pump inhibitors (omeprazole and lansoprazole) and H₂ receptor antagonists (famotidine, nizatidine, ranitidine, and cimetidine). Although generally considered to have a benign side-effect profile, these medications have been reported to cause serious neuropsychiatric complications—including mental confusion, agitation, depression, and hallucinations—mainly in geriatric patients with impaired hepatic-renal function.³⁶ These occur in only 37

Time to onset of psychiatric side effects from H₂ antagonists varies. Ranitidine can cause depression 4 to 8 weeks after treatment begins. Cimetidine has been reported to cause adverse events within 2 to 3 weeks and delirium within 24 to 48 hours.³⁸ These effects usually resolve within 3 days of discontinuing the drug. Cimetidine is also associated with sexual dysfunction.

Clinical Point

The acne drug isotretinoin can cause severe depression and suicidal behavior

Discontinuing ranitidine or cimetidine can induce a withdrawal syndrome that includes anxiety, insomnia, and irritability.³⁹ Cimetidine can increase the blood level and action of tricyclic antidepressants. Blood levels of these antidepressants can become toxic, resulting in tachycardia and other adverse effects.

Other medications. Ondansetron is a 5-hydroxytryptamine subclass 3 (5-HT₃) antagonist used for antiemetic therapy. In case reports, it has been strongly associated with anxiety.⁴⁰ This association is complex, however, and studies are evaluating 5-HT₃ receptor antagonists for the treatment of anxiety, depression, phobia, and schizophrenia.

Isotretinoin—a retinoid used for severe acne—can cause severe depression and suicidal behavior.⁴¹

Aminophylline and salbutamol are associated with agitation, insomnia, euphoria, and delirium. Methotrexate is known to cause personality changes, irritability, and delirium.²⁷

Box 2

Psychiatric effects of OTC and prescription analgesics

Up to 70% of persons in Western countries use analgesics regularly, primarily for headaches, other specific pains, and febrile illness. Nonsteroidal anti-inflammatory drugs (NSAIDs)—including aspirin, naproxen, ibuprofen, and indomethacin—are efficacious and have a wide safety margin, but potentially serious psychiatric side effects can occur even when these drugs are taken in recommended doses.

Salicylate intoxication, which can present as frank delirium, often goes unrecognized. Any NSAID can produce delirium in the elderly. Case reports have also implicated NSAIDs in mania, psychosis, and depressive disorders with suicidal ideation.³⁵

Opioids may cause sedation, psychic slowing, dysphoria, mood changes, psychosis, and delirium. Epidural administration of morphine may induce hallucinations and catatonia. Opioid antagonists—such as naloxone and, particularly, naltrexone—can induce dysphoria, fatigue, sleep disturbances, suicidality, hallucinations, and delirium. The serotonin 5-HT₁ agonist sumatriptan (an antimigraine medication) has been associated with fatigue, anxiety, and panic disorder.⁵

Skeletal muscle relaxants such as baclofen and dantrolene may induce sleep disturbances, anxiety, agitation, mood disturbances, hallucinations, and delirium.

Treating drug-related mood effects

If you suspect a nonpsychotropic medication is causing your patient’s psychiatric symptoms, discuss this with the patient and the prescribing physician. Switching to another similar agent may be an option. If this is not possible:

work closely with the patient’s primary physician
treat mood symptoms with appropriate psychotropics.

Related resources

Turjanski N, Lloyd GG. Psychiatric side-effects of medications: recent developments. Advances in Psychiatric Treatment 2005;11:58-70.
Brown TM, Stoudemire A. Psychiatric side effects of prescription and over-the-counter medications. Recognition and management. Washington, DC: American Psychiatric Publishing; 1998.
Physicians’ Desk Reference. www.pdr.net.

Drug brand name

Acyclovir • Zovirax
Aminophylline • Phyllocontin, Truphylline
Atenolol • Tenormin
Azatadine • Optimine
Baclofen • Lioresal
Chloramphenicol • Chloromycetin
Cimetidine • Tagamet
Ciprofloxacin • Cipro
Clarithromycin • Biaxin
Clonidine • Catapres
Cyclosporine • Neoral, Sandimmune, others
Dantrolene • Dantrium
Didanosine • Videx
Efavirenz • Sustiva
Ethionamide • Trecator
Famotidine • Pepcid
Foscarnet • Foscavir
Ganciclovir • Cytovene
Indomethacin • Indocin
Interferon alfa • Intron, Roferon
Isoniazid • Nydrazid
Isotretinoin • Accutane
Lansoprazole • Prevacid
Leuprolide • Lupron
Lidocaine • Xylocaine, Xylocard
Loratadine • Claritin
Methotrexate • Rheumatrex, Trexall
Methyldopa • Aldomet
Metoprolol • Lopressor
Mirtazapine • Remeron
Nafarelin • Synarel
Naloxone • Suboxone
Naltrexone • Vivitrol
Naphazoline • Naphcon-A, Clearine
Naproxen • Aleve, others
Nizatidine • Axid
Ofloxacin • Floxin
Omeprazole • Prilosec
Ondansetron • Zofran
Paroxetine • Paxil
Peginterferon alfa • PEG-Intron, Pegasys
Phenylephrine • Neo-Synephrine
Prednisolone • Blephamide, Pred Forte, others
Propranolol • Inderal
Pseudoephedrine • Actifed, Sudafed
Ranitidine • Zantac
Reserpine • Serpasi
Ribavirin • Copegus, Rebetol
Salbutamol • Aerolin, Airomir, others
Sertraline • Zoloft
Sumatriptan • Imitrex
Tenofovir • Viread
Trimethoprim • Proloprim

Disclosure

The authors report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.