Cognitive Function in Hypertensives Treated with Atenolol or Propranolol DIANE M. PALAC, MD, RICHARD D. CORNISH, PhD, WALTER J. McDONALD, MD, D. ANN MIDDAUGH, MD, DIANE HOWIESON, PhD, SUSAN P. BAGBY, MD Study ol~ecttve: To test reports that beta blockers, p a r t i c u larly lipophilic f o r m ~ i m p a i r cognitive f u n c t i o n a n d c a u s e p s y c h i a t r i c disturbances. Design: R a n d o m i z e d , double-blind, controlled c r o s s o v e r trial with eight-week treaOnent periods. Patients: Sequentia/sample o f 42 male veterans, with u n t r e a t e d diastolic b l o o d p r e s s u r e s ( D B P ) between 9 0 a n d 110 ~imHg~ aged 3 5 - 6 4 years. Interventions: Propranolol-LA, 80-rag tablets, o r atenoloL 50-rag tablets, were g i v e n daily, i n c r e m e n t e d by o n e tablet at weekly intervals u n t i l D B P 12 years Mean Creatinine Hydrochlorothiazide Baseline On first beta blocker Beta blocker (median) PropranoloI-LA Atenolol

Atenolol Group Drug 1 (n = 16)

44% 12.5 years 1.1 + 0.6 mg/dl

38% 12.6 years 1.1 + 0.6 mg/dl

28% 50%

43% 43%

240 rag/day 50 rag/day

240 rag/day 1O0 rag/day

side effects, and n o n c o m p l i a n c e largely a c c o u n t e d for the withdrawals. Thirty-four subjects c o m p l e t e d the study (Table 1). Of these, 18 were randomized to the treatment group Propranolol Drug 1. The remaining 16 were randomized to Atenolol Drug 1. The mean age of those completing the study was 53 years and the average duration of hypertension at entry was 7.5 years. Baseline b l o o d pressures and heart rates in the Pro-

Attention/Concentration/Reaction

Time

(Table Z) We e m p l o y e d five w i d e l y used tests to assess attention, concentration, and reaction time. These basic

cognitive functions were either unaffected or en-

TABLE Z Attention, Concentration, and Reaction Time Test Results Comparing the Drug-free Scores with ScoresObtained during Treatment with PropranoloI-LA and Atenolol Drug-free Randomization Group*

Drug

1

2

1

2

Digit Cancellation(no. correct) Propranolol Drug I t Atenolol Drug I t

42 42

42 45

36 36

36 37

Choice Reaction Time (sec.) Propranolol Drug 1 Atenolol Drug 1

15.1 15.2

14.7 14.6

15.2 15.3

15.3 14.8

7.4 7.4

8.3 7.3

8.3 7.2

8.4 7.2

8.4±1.9

7.4 6.7

7.6 6.8

7.7 6.4

8.2 6.8

6.5 + 2.0

7.9 7.1

8.0 7.4

7.6 7.2

8.2 7.8

9+3

WAIS Digit Span Forward Propranolol Drug 1 Atenolol Drug 1 Backward Propranolol Drug I Atenolol Drug 1 WAIS Digit Symbol (no. correct) Propranolol Drug 1 Atenolol Drug 1 Trail Making Form B (sec.) Propranolol Drug I t Atenolol Drug 1t

86 105

86 102

88 90

77 88

Norm

76 + 23

*For randomization group"Proprano[ol Drug 1," Drug 1 refers to propranolol-LA and Drug 2 refers to atenoloL For randomization group "Atenolol Drug 1," Drug 1 refers to atenolol and Drug 2 refers to propranoloI-LA. Actual test sequencewas Drug-free 1, Drug 1, Drug-free 2, then Drug 2. tDrug-free vs. drug, p < 0.05. Period 1 vs. period 2, p < 0.05 (Period 1 = the Drug-free 1, Drug 1 arm of the study; Period 2 = the Drug-free 2, Drug 2 arm; probable practice effect).

313

JOURNALOFGENERALINTERNALMEDICINE,Volume 5 (July/August), 1990 TABLE 3

Results of Memory Tests Comparingthe Drug-free Scoreswith Scores Obtainedduring Treatment with Propranolol-LAand Atenolol Drug-free Randomization Group* Rey Auditory Verbal LearningTest (AVLT) (total no. words recalled) PropranololDrug 1 Atenolol Drug 1

Drug

1

2

1

2

45 42

45 43

45 41

48 43

Norm

Rey AVLT (trials 5 - 6) PropranololDrug I f Atenolol Drug I t

2.1 2.9

1.6 2.2

1.6 2.1

1.8 2.7