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Home , Atenolol, Clonidine, Confusion, Depersonalization, Depression (mood), Emotional lability

Watch for nonpsychotropics causing psychiatric side effects

Look behind the scenes for drugs that play a supporting role in new symptoms

r. J, age 52, has a history of ® dependence.Dowden Health Media Four weeks after starting interferon therapy for Mhepatitis C, he presents to the outpatient clinic with depressedCopyright mood, ,For personal decreased use only energy, poor concentration, , , and . Because Mr. J has no history of , the psychia- trist diagnoses him with depressive disorder secondary to interferon. Interferon is stopped. Mr. J’s mood improves, hiatry but he wants to restart interferon. c The psychiatrist starts Mr. J on , 50 mg/d, then gradually increases the dose to 150 mg/d as Mr. J’s mood symptoms return. Subsequently, the patient continues in- terferon with a combination of sertraline and supportive . Blair kelly Blairfor Current kelly Psy

Recognizing a as the possible cause of your Kanwaldeep S. Sidhu, MD patient’s psychiatric symptoms can avoid inaccurate Third-year resident diagnosis and nonindicated psychiatric treatment. Dil- Richard Balon, MD Professor igently evaluating patients for drug-related psychiatric side effects is critical because complications usually are reversed when the offending drug is discontinued. Department of and Behavioral Neurosciences Wayne State University Unfortunately, a thin line separates available evidence Detroit, MI from anecdotal myths about psychiatric complications of nonpsychotropics. Almost two-thirds (65%) of drugs included in the Physicians’ Desk Reference list potential psychiatric side effects, according to a random sample review.1 In some patients, such as Mr. J, these effects can exacerbate mood symptoms and result in perceptual, cognitive, or Current Psychiatry behavioral disturbances. Vol. 7, No. 4 61 continued

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New-onset psychiatric symptoms? Check patient’s drug list Symptom Documented as a possible cause

Psychosis/ Anabolic androgenic steroids, , , ,

agitation , didanosine, , H2 blockers, isoniazid, nitrates, NSAIDs, Nonpsychotropic , proton pump inhibitors, quinolones, , skeletal muscle relaxants, sulfonamides/trimethoprim Acyclovir, anabolic androgenic steroids, clonidine, corticosteroids, cyclosporine,

decongestants, didanosine, 5-HT1 such as , foscarnet, ganciclovir, nitrates, ondansetron, penicillins, skeletal muscle relaxants

Depression Anabolic androgenic steroids, beta blockers, chloramphenicol, clonidine, corticosteroids, didanosine, , , foscarnet, GnRH agonists,

H2 blockers, interferons, isoniazid, , NSAIDs, quinolones, statins, Clinical Point ACE inhibitors, anabolic androgenic steroids, antibiotics (most), anticholinergics, beta blockers, centrally acting antihypertensives such as and Beta blockers such , , clonidine, corticosteroids, didanosine, digoxin, H2 blockers, as and , , nitrates, NSAIDs, opioids can Insomnia Aminophylline, anabolic androgenic steroids, clonidine, corticosteroids, decongestants, didanosine, opioid antagonists, proton pump inhibitors, quinolone cause delirium and antibiotics, salbutamol, skeletal muscle relaxants, tetracyclines

NSAIDs: nonsteroidal anti-inflammatory drugs; ACE: angiotensin-converting enzyme; GnRH: gonadotropin-releasing hormone Source: Prepared for Current Psychiatry by Drs. Sidhu and Balon from references cited in this article

A wide range of drugs can cause psycho- Metoprolol and propranolol can induce sis, agitation, anxiety, depression, delirium, delirium and psychosis.4,5 Psychiatric side or insomnia (Table). On the other hand, cer- effects with metoprolol are frequent,4 and tain psychiatric side effects of nonpsycho- propranolol has been associated with: tropics can be beneficial Box( 1). • sedation (affecting >10% of patients) Improve your assessments by examin- • ing the evidence linking psychiatric side • visual impairment effects to commonly prescribed and over- • the-counter (OTC) compounds, including: • delirium • cardiovascular medications • depression.5 • steroids (prescription and illegal) In 1967, it was reported that up to 50% • hormones of patients taking propranolol may experi- • interferons ence and at times severe depres- • antimicrobials. sion.6 These effects may occur acutely or develop gradually. 5 The relationship between depressive Cardiovascular medications symptoms and beta blockers has been in- Beta blockers have CNS effects—some of creasingly questioned, however. One study which cause psychiatric syndromes—that did not find a higher prevalence of depres- might depend on an ancillary property sion in patients receiving beta blockers vs such as lipophilicity.2 Unlike hydrophilic those receiving other medications, although agents such as that are excreted this trial had major methodologic limita- unchanged by the kidneys, lipophilic tions.7 One large study found no significant drugs such as metoprolol and propranolol association between beta-blocker use and are metabolized by the and are be- major depression, regardless of patient age, lieved to enter the brain. Metoprolol has a gender, or race.8 brain/plasma concentration ratio about 20 These studies the importance of Current Psychiatry 62 April 2008 times higher than that of atenolol.3 carefully assessing the individual patient before assigning neurotoxicity to beta block- Box 1 ers, as these drugs have considerable ben- efits for cardiovascular .9 Not all psychiatric side effects are harmful Angiotensin-converting enzyme (ACE) inhibitors also the CNS. About 4% n some instances, mood-elevating side effects of nonpsychotropic medications to 8% of patients taking an ACE inhibitor I might be beneficial. This might be the experience altered mental status—typically case if your patient experiences a sudden, increased and psychomotor activ- otherwise unexplainable improvement. ity—although <2% discontinue the medica- tion because of neuropsychiatric side effects. CASE Helped by corticosteroids These include: Ms. Q, age 44, has a history of and • anxiety major depressive disorder and is being • treated by a resident psychiatrist with • insomnia a combination of , 60 mg/d, • , 15 mg at night, and cognitive- • behavioral therapy. Her treatment has been Clinical Point • hallucinations.5 challenging, and the psychiatrist has tried Mood changes Sedation occurs in about 5% of patients multiple medications and psychotherapy modalities. are the most taking ACE inhibitors. Depression and sui- At a recent psychotherapy session, Ms. cide ideation as a result of ACE inhibition common psychiatric Q says she has been much better, have been reported;13 however, ACE inhibi- symptoms caused by with improved mood and greater energy. tors have also been known to improve de- Upon further questioning, she reports corticosteroids pression. Episodes of frank delirium have having an asthma exacerbation a week 5 been reported. before that resulted in hospitalization. During her stay, Ms. Q was started on Clonidine is a centrally acting alpha- a tapering dose of , which . The alpha- system regu- elevated her mood. Depressive symptoms lates arousal and has an important role in returned when the effects of the major depression, anxiety states, and other prednisone wore off. arousal disorders. Prednisone is not indicated for depression and has harmful effects when More than one-third (35%) of patients tak- used long term. The psychiatrist adds ing clonidine experience sedation or lethar- , 300 mg/d, to Ms. Q’s regimen, gy; less commonly, the drug causes anxiety and her symptoms improve. (3%), agitation (3%), depression (1%), and insomnia (1%).5 Acute , delirium, , and psychosis related to cloni- , but the evidence is inconclusive. dine use have long been recognized, occur- Some studies have supported this link,10,11 ring in <1% of patients—primarily those whereas others have strongly refuted it12,13 with preexisting cerebrovascular disease.5 or had mixed results.14 A recent review15 rec- ommends being vigilant for psychiatric side Other cardiovascular drugs. Side effects of effects in patients taking these drugs. nitrates/nitrites include delirium, psychosis (including ), anxiety, restlessness, agitation, and hypomania.5 Digoxin can Steroids: prescription and illegal cause cardiac glycoside-induced encepha- Corticosteroids are prescribed for a variety lopathy, which may present as sedation, of immune system-related , includ- , depression, and psychosis. Patients ing asthma, allergic , rheumatoid may develop delirium, even when digoxin/ arthritis, inflammatory bowel disease, and digitoxin serum levels are within a thera- dermatologic disorders. Mood changes are peutic range. the most common psychiatric symptoms -lowering statins might be caused by use; delirium is less Current Psychiatry linked to an increased risk of depression and common. Psychiatric side effects include: Vol. 7, No. 4 63 • lethargy cases or situations in which the dosage • insomnia cannot be reduced, the patient may require • or mood stabilizers.19 • depression Female gender and past psychiatric • psychosis history might be risk factors for develop- • “personality changes” ing psychiatric symptoms with cortico- • anxiety steroids,22 although not all studies have Nonpsychotropic • agitation.5 confirmed these findings.18 medications Multiple studies have linked cortico- steroids and mood symptoms. The Boston Anabolic androgenic steroids (AAS) have Collaborative Drug Surveillance Program16 limited therapeutic benefits but are used confirmed a direct relationship between illegally by some bodybuilders, wrestlers, corticosteroid dosage and psychiatric ef- and other amateur and professional ath- fects. More than 18% of patients had severe letes to increase muscle mass, enhance psychiatric symptoms at corticosteroid performance, and gain a competitive edge. dosages >80 mg/d. AAS can cause acute , delirium, Clinical Point A prospective study of asthma patients mania or hypomania, homicidal , ag- Some studies found statistically significant changes in gression, and extreme mood swings, as suggest a link mood—primarily manic symptoms—dur- well as a marked increase in , irrita- ing brief corticosteroid courses at modest bility, agitation, and . between dosages. Depressed persons did not be- In a large observational cohort study and depression but come more depressed during prednisone of 320 bodybuilding amateur and recre- in others estrogen therapy, however; in fact, some improved. ational athletes,23 AAS use induced many had a positive effect Some patients with posttraumatic stress of these psychiatric side effects. The extent disorder reported increased depression intensified as the abuse escalated. A study on mood and of the traumatic event dur- that used the Structured Clinical Interview ing prednisone therapy.17 for DSM-III-R to compare 88 athletes using In a study of 50 ophthalmologic pa- steroids with 68 nonusers found that 23% tients who did not have psychiatric illness of the AAS users reported major mood receiving (mean starting syndromes, including mania, hypomania, dose 119 mg/d) for 8 days, 26% developed and major depression.24 mania and 10% depression.18 None report- In a 2-week, double-blind, fixed-order, ed psychotic symptoms. -controlled, crossover study of healthy The most common adverse effects of male inpatient volunteers, AAS had both: short-term corticosteroid therapy are eu- • mood-elevating effects—euphoria (“ste- phoria and hypomania. Long-term therapy roid ”), increased energy, and increased tends to induce depressive symptoms.19 A sexual arousal and drive review of 79 cases of psychiatric syndromes • mood-dysphoric effects, such as irri- induced by corticosteroids found that 41% tability, mood swings, increasingly violent reported depression, 28% mania, 6% mixed , increased , and cognitive symptoms, and 14% psychosis.20 impairments.25 A group of 16 healthy volunteers receiv- As with corticosteroids, psychiatric ing 80 mg/d of prednisone over 5 days symptoms from AAS become more preva- exhibited depressed or elevated mood, ir- lent and severe as dosage increases. They ritability, lability, increased energy, anxiety, usually resolve within a few weeks after and depersonalization.21 Numerous case users discontinue steroids but may persist studies have reported anxiety, agitation, for up to 1 month, even if adequately treat- mania, and psychotic symptoms in children ed with medication. and adults taking inhaled corticosteroids. In general, psychiatric side effects of corticosteroids occur within 2 weeks of Hormones starting therapy and resolve with dosage Gonadotropin-releasing hormone (GnRH) Current Psychiatry 64 April 2008 reduction or discontinuation. In severe agonists such as leuprolide and nafarelin continued on page 68 continued from page 64 are approved for treating endometrio- neuropsychological syndromes. Neuropsy- sis, advanced prostate , precocious chiatric symptoms may be a characteristic of puberty, and uterine leiomyomata. Some hepatitis C, interferon treatment, or both.32 studies and case reports suggest that these agents cause depressive symptoms.26 Antimicrobial agents Progestins have complex and variable Antibiotic and antiviral drugs can cause Nonpsychotropic psychiatric effects. Clinical trials have in- psychiatric side effects: medications vestigated the effects of ex- • directly by affecting neuronal functions ogenous estrogens on psychiatric patients, • indirectly by entering the brain rapidly, but results have been inconsistent—pos- taking advantage of the compromised sibly because of small numbers of subjects blood-brain barrier during or and design flaws.26 Some studies suggest infection. a link between estrogen and depression in Delirium is the most common psychi- premenopausal and menopausal women atric complication associated with these with and without psychiatric illness, but agents.5 Clinical Point findings remain controversial because oth- Watch for depressive er studies have found that estrogens have Antibiotics. Penicillin and its analogues 26,27 symptoms in positive effects on mood. are associated with sedation, anxiety, and hallucinations. Delirium has been report- patients taking ed as a of most cephalosporins, interferon, especially Interferon especially in patients with compromised in those with a Various forms of interferon are used to renal function. Quinolones such as cipro- family history of treat hepatitis C, melanoma, multiple floxacin and ofloxacin rarely cause rest- sclerosis, chronic myelogenous leukemia, lessness, irritability, lethargy, tremors, mood disorders and other illnesses. Psychiatric complica- insomnia, mania, depression, psychosis, tions—particularly depression—are the delirium, , or (incidence most frequent side effect of interferon ≤1%).5 Though not commonly used, chlor- therapy and mainly occur within the first amphenicol may cause depression, con- 12 weeks of therapy.28 fusion, and delirium. Many case reports In a prospective observational study of have strongly associated clarithromycin veterans undergoing interferon-alfa/riba- with delirium.33 virin treatment for chronic hepatitis C: Isoniazid is one of the most commonly • 48% of patients not receiving psychiat- used antibiotics that can cause psychiatric ric care at baseline required treatment side effects; it has been linked to delirium, for neuropsychiatric side effects mania, depression, and psychosis. Ethion- • 23% developed symptoms of major amide is associated with sedation, irritabil- depression.29 ity, depression, restlessness, and psychosis. Treatment with a selective serotonin Tetracyclines have been known to cause stabilized these symp- depression, insomnia, and irritability at toms and allowed patients to continue high dosages. hepatitis treatment. Sulfonamides can cause delirium. Psy- Because patients who receive interferon chosis and confusion also have been re- are far more likely to require psychiatric ported, especially when sulfa drugs are intervention if they have a family history combined with trimethoprim.5 of mood disorders, closely monitor them for depressive symptoms and treat such Antivirals. When used intravenously and symptoms aggressively. Also closely moni- at high doses, acyclovir and ganciclovir can tor patients with multiple psychiatric diag- cause lethargy, anxiety, hallucinations, and noses receiving interferon-alfa therapy.30 frank delirium.5 Foscarnet—an antiviral Jeungling et al31 speculated that hypo- used to treat herpes viruses—can cause de- metabolism in the prefrontal cortex may pression, anxiety, hallucinations, and aggres- Current Psychiatry 68 April 2008 predispose patients to interferon-associated sive irritability. continued on page 72 continued from page 68 Didanosine—an antiretroviral agent to treat HIV infections—can cause lethargy (5% to 7% of patients), depression (2%), anxiety (2%), (25%), delirium (2%), insomnia (1%), and psychotic delusions (1%).5 Efavirenz treatment may be associ- ated with major depression and severe suicidal ide- ation.34 Tenofovir, a nucleotide reverse transcriptase inhibitor, has not been associated with psychiatric side effects.27

Antifungals. Psychiatric side effects are rare.

OTC and other agents Many common nonprescription agents can cause psychiatric symptoms. The most frequently used classes include cold and allergy preparations, reflux medications, and (Box 2).5,35

Cold preparations. Combined antihistamines and de- congestants—such as , azatadine, , , , pseudoephed- rine, and —can cause an -like psychosis that typically manifests as confusion, disori- entation, agitation, hallucinations, and prob- lems. Decongestants can cause dangerously high levels of when combined with inhibitors (MAOIs) and are contraindicated in patients taking MAOIs. Ephedrine can induce restless- ness, dysphoria, irritability, anxiety, and insomnia.

Reflux medications. Two primary classes of reflux medications are proton pump inhibitors ( and lansoprazole) and H2 receptor antagonists (famoti- dine, nizatidine, ranitidine, and cimetidine). Although generally considered to have a benign side-effect pro- file, these medications have been reported to cause seri- ous neuropsychiatric complications—including mental confusion, agitation, depression, and hallucinations— mainly in geriatric patients with impaired hepatic-renal function.36 These occur in only <0.2% of outpatients but are much more common among patients who are hos- pitalized, elderly, or have hepatic or renal failure.37

Time to onset of psychiatric side effects from H2 an- tagonists varies. Ranitidine can cause depression 4 to 8 weeks after treatment begins. Cimetidine has been re- ported 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. Ci- metidine is also associated with . Discontinuing ranitidine or cimetidine can in- duce a withdrawal syndrome that includes anxiety, insomnia, and irritability.39 Cimetidine can increase Box 2 Psychiatric effects of OTC and prescription analgesics

p to 70% of persons in Western countries Opioids may cause sedation, psychic Uuse analgesics regularly, primarily for slowing, dysphoria, mood changes, , other specific , and febrile psychosis, and delirium. Epidural illness. Nonsteroidal anti-inflammatory drugs administration of may induce (NSAIDs)—including , , hallucinations and catatonia. Opioid , and indomethacin—are efficacious antagonists—such as and, and have a wide safety margin, but potentially particularly, naltrexone—can induce serious psychiatric side effects can occur dysphoria, fatigue, sleep disturbances, even when these drugs are taken in suicidality, hallucinations, and delirium. The

recommended doses. serotonin 5-HT1 agonist sumatriptan (an Salicylate intoxication, which can present antimigraine medication) has been associated as frank delirium, often goes unrecognized. with fatigue, anxiety, and disorder.5 Any NSAID can produce delirium in the Skeletal muscle relaxants such as elderly. Case reports have also implicated and dantrolene may induce sleep NSAIDs in mania, psychosis, and depressive disturbances, anxiety, agitation, mood Clinical Point disorders with suicidal ideation.35 disturbances, hallucinations, and delirium. Combined antihistamines and the blood level and action of an- • treat mood symptoms with appropri- decongestants can tidepressants. Blood levels of these anti- ate psychotropics. cause psychosis can become toxic, resulting in References and other adverse effects. 1. Smith DA. Psychiatric side effects of non-psychiatric drugs. S D J Med 1991;44(10):291-2. 2. Conant J, Engler R, Janowsky D, et al. Other medications. Ondansetron is a 5- side effects of beta-adrenergic blocking agents with high and hydroxytryptamine subclass 3 (5-HT ) an- low solubility. J Cardiovasc Pharmacol 1989;13:656-61. 3 3. Cruickshank JM, Neil-Dwyer G. Beta-blocker brain tagonist used for antiemetic therapy. In case concentrations in man. Eur J Clin Pharmacol 1985;28:21-3. 4. Sirois FJ. Visual hallucinations and metoprolol. Psychosomatics reports, it has been strongly associated with 2006;47(6):537-8. anxiety.40 This association is complex, how- 5. Brown TM, Stoudemire A. Psychiatric side effects of prescription and over-the-counter medications. Recognition and management. ever, and studies are evaluating 5-HT3 recep- Washington, DC: American Psychiatric Publishing; 1998. tor antagonists for the treatment of anxiety, 6. Waal HF. Propranolol-induced depression (letter). Br Med J 1967;2:50. depression, , and . 7. Carney RM, Rich MW, teVelde A, et al. Prevalence of major depressive disorder in patients receiving beta-blocker therapy Isotretinoin—a retinoid used for severe versus other medications. Am J Med 1987;83(2):223-6. —can cause severe depression and 8. Bright RA, Everitt DE. Beta-blockers and depression. Evidence 41 against an association. JAMA 1992;267(13):1783-7. suicidal behavior. 9. Yudofsky SC. Beta-blockers and depression: the clinician’s Aminophylline and salbutamol are as- dilemma. JAMA 1992;267:1826-7. 10. Law MR, Thompson SG, Wald NJ. Assessing possible hazards sociated with agitation, insomnia, eupho- of reducing serum cholesterol. BMJ 1994;308:373-9. ria, and delirium. Methotrexate is known 11. Morales K, Wittink M, Datto C, et al. causes changes in affective processes in elderly volunteers. J Am to cause personality changes, irritability, Geriatr Soc 2006;54(1):70-6. 27 12. Yang CC, Jick SS, Jick H. Lipid-lowering drugs and the and delirium. risk of depression and suicidal behavior. Arch Intern Med 2003;163(16):1926-32. 13. Callréus T, Agerskov Andersen U, Hallas J, et al. Cardiovascular drugs and the risk of suicide: a nested case-control study. Eur Treating drug-related J Clin Pharmacol 2007;63(6):591-6. 14. Agostini JV, Tinetti ME, L, et al. Effects of statin use on mood effects muscle strength, , and depressive symptoms in older adults. J Am Geriatr Soc 2007;55(3):420-5. If you suspect a nonpsychotropic medica- 15. Tatley M, Savage R. Psychiatric adverse reactions with statins, tion is causing your patient’s psychiatric fibrates and ezetimibe: implications for the use of lipid- lowering agents. Drug Saf 2007;30(3):195-201. symptoms, discuss this with the patient 16. Boston Collaborative Drug Surveillance Program. Acute adverse reactions to prednisone in relation to dosage. Clin and the prescribing physician. Switching Pharm Ther 1972;13:694-8. to another similar agent may be an option. 17. Brown ES, Suppes T, Khan DA, Carmody TJ 3rd. Mood changes during prednisone bursts in outpatients with asthma. If this is not possible: J Clin Psychopharmacol 2002;22:55-61. • work closely with the patient’s 18. Naber D, Sand P, Heigl B. Psychological and neuropsychological effects of 8 days’ corticosteroid treatment. A prospective study. Current Psychiatry primary physician 1996;21:25-31. Vol. 7, No. 4 73 continued 19. Warrington TP, Bostwick JM. Psychiatric adverse effects of corticosteroids. Mayo Clin Proc 2006;81(10):1361-7. Related Resources 20. Lewis DA, Smith RE. Steroid-induced psychiatric syndromes: a report of 14 cases and a review of the literature. J Affect • Turjanski N, Lloyd GG. Psychiatric side-effects of Disord 1983;5:319-32. medications: recent developments. Advances in Psychiatric 21. Wolkowitz OM, Rubinow D, Doran AR, et al. Prednisone Treatment 2005;11:58-70. effects on neurochemistry and behavior. Arch Gen Psych 1990;47:963-8. • Brown TM, Stoudemire A. Psychiatric side effects of prescription and over-the-counter medications. Recognition 22. Ling MHM, Perry PJ, Tsuang MT. Side effects of corticosteroid therapy. Arch Gen Psychiatry 1981;38:471-7. and management. Washington, DC: American Psychiatric Publishing; 1998. 23. Pagonis TA, Angelopoulos NV, Koukoulis GN, Nonpsychotropic Hadjichristodoulou CS. Psychiatric side effects induced • Physicians’ Desk Reference. www.pdr.net. medications by supraphysiological doses of combinations of anabolic steroids correlate to the severity of abuse. Eur Psychiatry Drug Brand Names 2006;21(8):551-62. Acyclovir • Zovirax Methyldopa • Aldomet 24. Pope HG Jr, Katz DL. Psychiatric and medical effects of Aminophylline • Phyllocontin, Metoprolol • Lopressor anabolic-androgenic steroid use: a controlled study of 160 athletes. Arch Gen Psychiatry 1994;51:375-82. Truphylline Mirtazapine • Remeron 25. Su T, Pagliaro M, Schmidt P, et al. Neuropsychiatric effects Atenolol • Tenormin Nafarelin • Synarel of anabolic steroids in male normal volunteers. JAMA Azatadine • Optimine Naloxone • Suboxone 1993;269:2760-4. Baclofen • Lioresal Naltrexone • Vivitrol 26. Warnock JK, Bundren JC, Morris DW. Depressive symptoms Chloramphenicol • Naphazoline • Naphcon-A, associated with gonadotropin-releasing hormone agonists. Chloromycetin Clearine Depress Anxiety 1998;7:171-7. Cimetidine • Tagamet Naproxen • Aleve, others Clinical Point 27. Turjanski N, Lloyd GG. Psychiatric side-effects of medications: Ciprofloxacin • Cipro Nizatidine • Axid recent developments. Advances in Psychiatric Treatment Clarithromycin • Biaxin Ofloxacin • Floxin The acne drug 2005;11:58-70. Clonidine • Catapres Omeprazole • Prilosec 28. Lotrich FE, Rabinovitz M, Gironda P, Pollock BG. Depression Cyclosporine • Neoral, Ondansetron • Zofran isotretinoin can following pegylated interferon-alpha: characteristics and Sandimmune, others Paroxetine • Paxil vulnerability. J Psychosom Res 2007;63(2):131-5. Dantrolene • Dantrium Peginterferon alfa • cause severe 29. Dieperink E, Ho SB, Thuras P, Willenbring ML. A prospective Didanosine • Videx PEG-Intron, Pegasys study of neuropsychiatric symptoms associated with Efavirenz • Sustiva Phenylephrine • interferon-alpha-2b and ribavirin therapy for patients with depression and chronic hepatitis C. Psychosomatics 2003;44(2):104-12. Ethionamide • Trecator Neo- Famotidine • Pepcid Prednisolone • Blephamide, suicidal behavior 30. Jakiche A, Paredez EC, Tannan PK, et al. Trend of depression and the use of psychiatric medications in U.S. Veterans with Foscarnet • Foscavir Pred Forte, others hepatitis C during interferon-based therapy. Am J Gastroenterol Ganciclovir • Cytovene Propranolol • Inderal 2007;102(11):2426-33. Indomethacin • Indocin • Actifed, 31. Juengling FD, Ebert D, Gut O, et al. Prefrontal cortical Interferon alfa • Intron, Sudafed hypometabolism during low-dose interferon alpha treatment. Roferon Ranitidine • Zantac (Berl) 2000;152:383-9. Isoniazid • Nydrazid Reserpine • Serpasil 32. Matthews SC, Paulus MP, Dimsdale JE. Contribution of Isotretinoin • Accutane Ribavirin • Copegus, Rebetol functional neuroimaging to understanding neuropsychiatric Lansoprazole • Prevacid Salbutamol • Aerolin, side effects of interferon in hepatitis C. Psychosomatics Leuprolide • Lupron Airomir, others 2004;45(4):281-6. Lidocaine • Xylocaine, Sertraline • Zoloft 33. Ozsoylar G, Sayin A, Bolay H. Clarithromycin monotherapy- Xylocard Sumatriptan • Imitrex induced delirium. J Antimicrob Chemother 2007;59(2):331. Loratadine • Claritin Tenofovir • Viread 34. Puzantian T. Central nervous system adverse effects with efavirenz: case report and review. Pharmacotherapy Methotrexate • Rheumatrex, Trimethoprim • Proloprim 2002;22:930-3. Trexall 35. Browning CH. Nonsteroidal anti-inflammatory drugs Disclosure and severe psychiatric side effects. Int J Psychiatry Med 1996;26(1):25-34. The authors report no financial relationship with any 36. Picotte-Prillmayer D, DiMaggio JR, Baile WF. H2 blocker company whose products are mentioned in this article or delirium. Psychosomatics 1995;36(1):74-7. with manufacturers of competing products. 37. Cantu TG, Korek JS. Central nervous system reactions to -2 receptor blockers. Ann Intern Med 1991;114:1027-34. 38. Bernstein J. Handbook of drug therapy in psychiatry. St. Louis, 40. Mitchell KE, Popkin MK, Trick W, Vercellotti G. Psychiatric MO: Mosby; 1995:380-1. complications associated with ondansetron. Psychosomatics 39. Rampello L, Nicoletti G. [The H2-antagonist 1994;35(2):161-3. therapy withdrawal syndrome: The possible role of 41. Brasic JR. people treated with isotretinoin for hyperprolactinemia]. Medicina (Firenze) 1990;10:294-6. depression. Psychol Rep 2007;100(3 Pt 2):1312-4.

Bottom Line Always investigate whether any changes in prescription or over-the-counter (OTC) medications could be causing your patients’ new psychiatric symptoms. Be especially vigilant for common culprits such as beta blockers, ACE inhibitors, corticosteroids, interferon, analgesics, isotretinoin, and OTC reflux drugs. Most psychiatric complications can be reversed by discontinuing the offending drug or replacing it with a different Current Psychiatry 74 April 2008 medication. Consult the prescribing physician before making a medication change.