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Tricyclic Antidepressants

  • Chapter
Antidepressants: Past, Present and Future

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 157))

Abstract

The first truly effective antidepressants were the tricyclics (TCAs) such as imipramine and amitriptyline. Many more followed in the 1960s and 1970s, before they were partly superseded by newer drugs such as the selective serotonin reuptake inhibitors (SSRIs). TCAs were discovered serendipitously, their clinical potential discerned, and their pharmacology was later elucidated. The first members of the class were three-ringed in chemical structure, but later compounds were more varied chemically. They act to increase biogenic amines in the brain, especially serotonin, norepinephrine and sometimes dopamine. The mechanism is to block reuptake back into the pre-synaptic neuron. They have a gradual onset of action and help about 60%–80% of depressed patients. However, they seem most effective in patients of moderate degrees of severity of illness. Some correlation between plasma concentration and clinical response has been established but this is of limited clinical application.

The TCAs have a wide range of unwanted effects, involving many bodily systems. Some induce drowsiness, some alertness. The convulsive threshold is lowered. The most troublesome side effects are autonomic, with dry mouth, constipation, blurring of vision, hypotension and tachycardia. Urinary retention occasionally occurs in elderly males. Adherence to treatment may be disappointingly low because of intolerability. A further major disadvantage is toxicity in overdose. Drug interactions involve other CNS drugs, especially sedatives and alcohol.

In clinical usage, the TCAs are given in the acute phases of depression and continued into the maintenance phase. They are also indicated as prophylactic therapy in patients prone to recurrent episodes. Patients with depression secondary to a dementing process often respond well to small doses.

The TCAs are still widely used, particularly in primary care, but mainly for reasons of cost. In most countries, secondary care practitioners prefer SSRIs because of their better side-effect profile and superior safety.

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  1. Institute of Psychiatry, King's College, Denmark Hill, London, SE5 9AF, UK

    M. Lader

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  1. Department of Psychiatry and Behavioral Sciences, University of Kansas School of Medicine and Psychiatric Research Insitute, 1010 N. Kansas, Wichita, Kansas, 67214, USA

    Sheldon H. Preskorn

  2. Feighner Research Institute, 5230 Carrol Canyon Rd # 220, San Diego, CA, 92121, USA

    John P. Feighner (President and Director of Research) (President and Director of Research)

  3. W8057 Moonlite Road, Neillsville, WI, 54456, USA

    Christina Y. Stanga

  4. Ross Editorial, 228 Black Rock Mtn Ln, Independence, VA, 24348, USA

    Ruth Ross

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Lader, M. (2004). Tricyclic Antidepressants. In: Preskorn, S.H., Feighner, J.P., Stanga, C.Y., Ross, R. (eds) Antidepressants: Past, Present and Future. Handbook of Experimental Pharmacology, vol 157. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-18500-7_7

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  • DOI: https://doi.org/10.1007/978-3-642-18500-7_7

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