Psychiatric side effects associated with the ten most commonly dispensed prescription drugs: a review

Journal of Family Practice, August, 1991 by John R. Hubbard, James L. Levenson, Graham A. Patrick

Drugs used to treat medical illness frequently cause psychiatric symptoms or side effects. Careful assessment of possible drug side effects is important to (1) determine whether the condition may be readily reversible by discontinuing the use of a specific drug, (2) avoid inaccurate diagnosis leading to nonindicated psychiatric treatment including additional drug therapy, and (3) identify and characterize previously unrecognized adverse drug effects. Psychiatric side effects of drugs are frequently cited in the Physicians' Desk Reference (PDR) and other sources, but there is little or no information on supporting documentation and frequency. The purpose of this review is to examine critically the potential psychiatric side effects of the ten most commonly dispensed drugs. The literature was systematically reviewed (with emphasis on studies conducted in the last 5 years) and a list was formulated of the adverse psychiatric side effect(s) for each drug. An accompanying scale (the literature support scale) was devised to indicate the degree of scientific support for the reported effect. A concise discussion also clarifies the strengths and weaknesses of the support for the occurrence of each adverse effect. The frequency of the reported side effect(s) is provided whenever possible but is often not available or is imprecise (often reflecting certain subpopulations of patients). In addition to the information provided in this review, more subtle psychiatric side effects may go largely unreported.

Methods

A list of the ten drugs (new and refill prescriptions) most often prescribed in 1988 was taken from the Pharmacy Times top 200 drugs of 1988 (Table 1). Two computer literature search systems were used to find the pertinent studies or observations related to psychiatric side effects of these ten drugs: MEDLINE (years 1984 to 1989) and Psyclit (years 1974 to 1989). Some articles were found in more recent publications. Although trade names were used by the Pharmacy Times,[1] the literature search was based on the generic active ingredients (which arc also listed in Table 1). A literature support scale presented in Table 2 was devised to summarize the weight of scientific evidence supporting each side effect, reflected by the number of asterisks. The most important potential psychiatric side effects are summarized in Table 3.

Commonly Prescribed Drugs

Amoxil

GENERIC-AMOXICILLIN

OTHER COMMON BRAND NAMES-ROBAMOX, TRIMOX (AND OTHERS)

General Information. Amoxicillin is commonly administered at a dose of 250 to 500 mg every 8 hours for adult patients and 20 to 40 mg per kg of body weight every 24 hours for pediatric patients. This semisynthetic penicillin is a bacterial agent that inhibits bacterial cell wall synthesis. Penicillin, therefore, has little effect on eukaryotic cells, which have no cell wall, intracellular organisms, or dormant microorganisms.[2] Clavulanic acid, which is combined with amoxicillin in products such as Augmentin, passes through the cell wall and acts as an inhibitor of beta-lactamase.[3]

POTENTIAL PSYCHIATRIC SIDE EFFECTS

** Hallucinations

** Confusion

** Mania

Discussion. Overall, there has been little convincing evidence that psychiatric side effects should be a major concern when prescribing amoxicillin. Behavioral changes, including confusion, mania, and hallucinations, may occur rarely in a few susceptible individuals.[4] For example, case reports in 1984 and 1986 found apparent onset of auditory hallucinations with or without visual hallucinations upon start of amoxicillin therapy.[5,6] The 1986 report also noted confusion and manic symptoms in a 30-year-old black woman.[5] This patient had a similar episode when placed on amoxicillin 14 years previously but had no psychiatric reactions to other antibiotics including nonaminobenzyl penicillins. Reversal of symptoms was achieved 9 to 12 days after termination of amoxicillin use.[5] The long time required for recovery after discontinuation of the drug in this case makes a causal relationship more uncertain. In a 1984 case report, interpretation of the cause of visual and auditory hallucinations in an elderly patient was complicated by the patient's cyclothymic history and possible (but clinically inapparent) hypoxia secondary to pneumonia.[6] The hallucinations stopped within 24 hours of drug discontinuation.

In addition to the reports cited above, hyperactivity accompanied by aggressiveness, crying, and insomnia was reported in four children using the closely related drug amoxicillin-clavulanate.[7] Similar effects recurred in a 10-year-old child after restarting amoxicillin-clavulanate 2 months later.[8] It is not known whether amoxicillin alone has these effects on children. While psychotic and anxiety symptoms have been reported with a 0.3% incidence with procaine-penicillin, they were apparently due to the procaine component.[9]

Lanoxin

GENERIC-DIGOXIN

General Informantion. Digoxin is commonly used at a dose of 0.50 to 0.75 mg followed by 0.25 mg every 6 to 8 hours (to a total dose of 1.0 to 1.5 mg). Intravenous or intramuscular injections are given at an initial dose of 0.25 to 0.5 mg, then 0.25 mg every 4 to 6 hours to a total dose of 1.0 mg). Maintenance doses are given at 0.125 to 0.5 mg per day orally or 0.125 to 0.250 per day intravenously or intramuscularly. Adjustments in dosage must take into account age, renal function, and lean body mass.[10] The usual pediatric maintenance dose is 10[mu]/kg administered every 12 hours.[11] Digoxin is used primarily in the treatment of congestive heart failure, atrial fibrillation, atrial flutter, and paroxysmal atrial tachycardia.[11] Digoxin increases myocardial contractile force (inotropic effect) by reversible inhibition of sarcolemma Na,K-ATPase, causing enhanced calcium influx.[2,3,11] Digoxin also lowers the conduction rate of the AV node by indirectly increasing parasympathetic tone and depressing sympathetic tone.[3] Potentially severe cardiac consequences, including heart block and arrhythmias, are well-recognized adverse effects.[5,6] In addition, nausea, headache, fatigue, anorexia, abdominal pain, vomiting, and abnormal color perception have been noted.[5,6]