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Simon J. C. Davies, MBBS, MRCPsych; Peter R. Jackson, PhD, FRCP; Lawrence E. Ramsay, MBChB, FRCP; Parviz Ghahramani, PharmD, PhD

Arch Intern Med. 2003;163:592-600.

Background  Poor adherence to antihypertensive drug regimens is common and may increase the risk for cardiovascular morbidity and mortality. Adverse effects of the drugs can contribute to poor adherence, but some patients who discontinue several different antihypertensive drugs may misinterpret nonspecific symptoms as adverse effects of the drug because of psychiatric morbidity. We examined the relationship between intolerance to antihypertensive drugs and the presence of panic disorder, panic attacks, anxiety, and depression.

Methods  We included all patients with hypertension who attended a hospital hypertension clinic during 1 year with at least 2 episodes of intolerance (resulting in reduction of the dosage or stopping an antihypertensive drug) recorded on standardized problem lists and a similar number of patients with no recorded episodes of intolerance. Psychiatric morbidity, assessed by self-administered questionnaires, was analyzed against the number of episodes of nonspecific and drug-specific intolerance, verified by means of individual case-note scrutiny, and scored independently by 2 assessors masked to patient identity.

Results  Analyzable questionnaires were returned by 233 (84%) of 276 patients who had experienced 576 (85%) of 679 episodes of intolerance assessed. Five hundred thirty-two episodes (92%) were subjective (patient was symptomatic); of these, 284 were judged to be drug specific; 248, nonspecific. Having more episodes of nonspecific intolerance was associated with significantly higher diastolic blood pressure (P = .003). Episodes of nonspecific intolerance were associated with panic attacks (P = .008), anxiety (Hospital Anxiety and Depression Scale score, P = .04), and depression (Hospital Anxiety and Depression Scale score, P = .005). Drug-specific intolerance was not associated with psychiatric morbidity.

Conclusions  Intolerance to multiple antihypertensive drugs, particularly non–drug-specific intolerance, is strongly associated with psychiatric morbidity. Physicians treating hypertensive patients need to recognize and manage the psychiatric aspects of intolerance to multiple antihypertensive drugs.

From the Psychopharmacology Unit, School of Medical Sciences, University of Bristol, Bristol (Dr Davies) and Clinical Pharmacology and Therapeutics, Royal Hallamshire Hospital, Sheffield (Drs Jackson, Ramsay, and Ghahramani), England.

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