Beta-adrenergic Blockade and Anxiety

611

beta blockade is a more likely mechanism for these drugs’ action in anxiety than any central effects they may have. Dextro-propranolol has only a sixtieth of the beta-blocking activity of the racemic form and is not beneficial in anxiety states.7 Therefore the beta-blocking activity is probably responsible for propranolol’s efficacy. Practolol, a "cardioselective" beta-blocker, gives much the same improvement in anxiety states as racemic propranolol,8 but very little practolol gets into the brain. This points to a peripheral, rather than central, effect. In fact, beta-blockers seem to have few central effects in man. Visual hallucinations have been reported in 2-3% of subjects who have taken propranolol, but the doses were usually high. Propranolol has sedative9 and anticonvulsive properties in some species, but other beta-blockers seem to stimulate the central nervous

Peripheral

THE LANCET

Beta-adrenergic Blockade and Anxiety OvER two thousand articles have been published on the clinical aspects of beta-adrenergic blockade and a decade has passed since GRANVILLE-GROSSMAN and TURNER1 undertook the first definitive study into the effects of beta blockade in psychiatric patients. In a monograph just published,2 TYRER points out that the findings of GRANVILLE-GROSSMAN and TURNER (on the efficacy of beta blockade in pathological anxiety states) have been frequently misinterpreted. In their con-

trolled, within-patient

study they showed that propranolol, 80 mg a day in divided doses, was more effective than placebo in relieving signs and symptoms of anxiety; but only autonomically mediated anxiety symptoms improved significantly, This does not mean that propranolol, or any other beta-adrenergic blocker yet studied, is an effective anti-anxiety drug. Studies with betablockers in normal subjects indicate that these drugs do not protect against induced anxiety,3 nor against lactate-induced anxiety or tachycardia,4 and in pathological anxiety states beta blockade is more effective in patients with predominantly somatic symptoms than in those whose primary experience is psychic anxiety.5 The importance of beta-adrenergic blockade to the understanding of anxiety derives from the fact that the sympathetic nervous system is activated in cross-over

anxiety, and beta blockade modifies

some

of the

bodily responses to this activation. Studies of pharmacological effects of beta-blockers in anxiety must always be related back to the subjective reported experience of anxiety or fear. No matter how elaborate our measurements, in the end we have to ask the subject how he is feeling.6 Selective blocking of somatic effects of anxiety is mainly useful if the source of anxiety is also thereby affected. In other words, there should be interruption of a somato-psychic sequence of events whereby the somatic symptom is contributing to maintenance of the anxiety. A useful effect in anxiety can be expected if there is clinical evidence that inappropriate sympathetic activity is contributing to the distress and anxiety. 1. Granville-Grossman, K. L., Turner, P. Lancet, 1966, i, 788. of Bodily Feeling in Anxiety (Maudsley Monograph no. 23). By PETER TYRER. London: Oxford University Press. 1976. Pp. 125. £6.50. 3. Eliash, H., Lager, C. G., Norrbäck, K., Rosen, A., Scott, H. Forsvarmedicin, 1967, 3,suppl. 2., p. 120. 4. Arbab, A. G., Bonn, J. A., Hicks, D. C. Br. J. Pharmac. 1971, 41, 430P. 5 Tyrer,P J., Lader, M. H. Br. med. J. 1974, ii, 14. 6 Lader, M. H. Br. J. Psychiat. 1973, spec. publ. no. 3, p. 53.

2. The Role

system. There is much evidence for increased catecholamine turnover and excretion in states of high arousal described as stressful or anxiety-provoking, 10 and psychiatric patients may have higher catecholamine-excretion rates than controls." Tremor associated with increased catecholamine secretion is blocked by racemic propranolol, as is increased physiological tremor. 12 In one investigation the emotional increase in tremor produced by mental arithmetic was not attenuated by propranolol, 13 but others showed that tremor in anxiety states is reduced more by propranolol than by saline14 or placebo, is The experimental evidence that beta blockade ameliorates the tremor due to increased sympathetic activity is in keeping with clinical

experience. What of cardiovascular symptoms? In general, non-anxious individuals infused with adrenaline are conscious of tachycardia but have little fear, whereas anxiety-prone patients in the same situation report anxiety and panic as well as tachycardia. Beta blockade is useful in the syndromes variously named as neurocirculatory asthenia, soldier’s heart, vasoregulatory asthenia, and hyperkinetic-heart syndrome. All these are probably types of anxiety state in which different clinical features predominate but which have in common increased cardiac output, supraventricular tachycardia, and labile hypertension. Many workers have found beta-blockers helpful in the "functional" heart conditions, and TYRER 16 explains why so 7. Bonn, J. A., Turner, P. Lancet, 1971, i, 1355. 8. Bonn, J. A. Turner, P., Hicks, D. C. ibid. 1972, i, 814. 9. Bainbridge, J. G., Greenwood, D. T. Neuropharmacology, 1971, 10, 453. 10. von Euler, U. S., Lundberg, J. J. appl. Physiol. 1954, 6, 551. 11. Regan, P. F., Reilly, J. J. nerv. ment. Dis. 1958, 127, 12. 12. Marsden, C. D., Foley, T. H., Owen, D. A. L., McAllister, R. G. Clin. Sci. 1967, 33, 53. 13. Marsden, C. D., Owen, D. A. L. Neurology, 1967, 17, 711. 14. Marsden, C. D., Gimlette, T. M. D., McAllister, R. G., Owen, D. A. L., Miller, T. N. Acta endocr., Copenh. 1968, 57, 353. 15. Tyer, P. J., Lader, M. H. Archs gen. Psychiat. 1974, 31, 506. 16. Tyrer, P. The Role of Bodily Feelings in Anxiety (Maudsley monogr. no. 23), p. 20. London, 1976.

612

many of these conditions have been described

as if entities: condition seems to each they separate have two parts-a disorder of cardiac function with appropriate symptoms and signs, and a diffuse mixture of symptoms which are due to anxiety. The latter group includes palpitations, dyspnoea, dizziness, weakness, lassitude, emotional lability, and hyperventilation. Preponderance of one or more of these symptoms accounts for the variation in adject;.ves used to designate the disorders. TYRER states that the anxious patients helped most by betablockers are those with mainly somatic complaints mediated by sympathetic activity-e.g., palpi-

Cataract Surgery

were

tation, trembling, giddiness, dizziness, shaking, or blushing. Sweating, muscle tension, headache, dry mouth, nausea, frequency of micturition, and diarrhoea are less affected by beta blockade. These last symptoms are not readily connected with the physiological activity of the beta-blockers. Patients in whom the first group of symptoms are virtually

primary events, with anxiety complained of as secondary or consequential, may do well on betablockers alone. In contrast are those patients with primarily psychic anxiety, marked by forebodings and dread. They too complain of bodily symptoms, but the correlation between bodily symptoms and physiological changes seems to be low; in other words, bodily symptoms may not reflect true physiological changes in this group. Patients with primarily psychic anxiety are not much helped by beta-blockers-indeed, they may get worse on them. There is still no evidence that sympathetic activation is reduced by beta blockade in stress; therefore it is not surprising that subjective anxiety is little affected. In some of these patients the bodily symptoms may have reassurance value and their abolition may make matters worse ("because I did not get the palpitations when I got the panic I was sure I was going to die"). Patients need to be carefully selected for treatment with beta-blockers, and they must be warned of the expected effects. For those patients with primarily somatic anxiety, beta-blockers are drugs of choice. In the

usual

therapeutic dose-range they have few side-

effects and there is little chance of drowsiness, tolerance, dependence, or abuse. Beta-blockers may be combined with centrally acting anxiolytics. In clinical practice, a flexible approach to dosage is important. Almost all beta-blockers are structurally

related

to isoprenaline, a potent beta-adrenergic agonist. Beta-blockers act by competitive antagonism with endogenous catecholamines at the receptor sites. The "sympathetic tone" will vary between patients, as will the speed of metabolic inactivation of the drug. Therefore it is best to start treatment with a low-dose regimen-say, 10-20 mg propranolol three or four times a day-knowing that this may have to be increased for the best therapeutic response.

CATARACT is the commonest cause of blindness; and cataract removal is said to be the oldest operation in the history of surgery. In the early days, this was achieved simply by knocking it backwards with a needle thrust through the limbus, so that it fell to the bottom of the vitreous, and this operation of "couching", which dated from the third millennium B.C., is still performed extensively, albeit damagingly, in remoter areas of the underdeveloped world. But, since 1748, "extraction" of the cataract gradually became the accepted method: the eyeball was incised along with the corneoscleral junction, and the opaque lens was lifted out, Until the 19403 it was thought safer to remove only the opaque lens nucleus; but nowadays the lens is nearly always removed complete with its tenuous

capsule (an "intracapsular extraction") through a wider incision involving nearly the half-circumference of the corneo-scleral margin. The actaal extraction has been rendered much simpler by the use of a freezing probe; this grips a frozen segment of the lens substance, whereas the traditional forceps can grasp only its very thin and friable capsule. And the operation has become much safer with the advent of ultrafine needles and suture materials ( 10 0 nylon or 8 - 0 "virgin" silk) which can close the wound so securely that patients are now allowed out of bed the day after operation, and can leave hospital a few days later. Thus the standard cataract operation nowadays consists of a wide corneo-scleral incision, which will be reunited by multiple fine buried sutures beneath a previously prepared conjunctival flap; a peripheral iridectomy; and withdrawal of the whole lens by forceps, or, if available, a freezing probe, Over 90% of such patients can thereafter read small print through their aphakic spectacles. This admirable operation, elegant and economical in time and equipment, has the major drawback of leaving the patient dependant on clumsy aphakic spectacles. In order to avoid this limitation, intraocular lens implants were first seriously introduced in 1950 (spirited, but disastrous, attempts date back centuries earlier). Since then, each year has seen the evolution of new lens-shapes and fixation techniques, but the high morbidity-rate continues to discourage their general acceptance, and with the currently favoured lenticuli held by clips or sutures to the pupil margins even the immediate

postoperative complications (especially macular oedema) are all too frequent and a long-term follow-up is still awaited. (It was not until the fourth fifth year that most of BARRAGUER’s 400 implants had to be removed because of chronic irrItation. 1) The disadvantages of heavy aphakic spectacles are obvious, but the solution may well lieir. improved forms of contact lenses, rather thanir. or

1.

DeVoe, A. Am. J. Ophthal. 1976, 81, 715.