Hostname: page-component-8448b6f56d-t5pn6 Total loading time: 0 Render date: 2024-04-23T15:19:09.462Z Has data issue: false hasContentIssue false

Overdose of Tricyclic Anti-Depressants and Deductions Concerning their Cerebral Action

Published online by Cambridge University Press:  29 January 2018

S. A. Lewis
Affiliation:
Lecturer
Ian Oswald
Affiliation:
Senior Lecturer

Extract

The tricyclic antidepressant drugs are established therapeutic agents, yet their mode of action has remained obscure. The usual delay of some 10 or more days before they produce beneficial effects has never been satisfactorily explained. Many months are usually necessary for lasting cure, for often symptoms recur when the drugs are stopped. If they are then reinstated for several months, and then stopped, the patient commonly remains free of symptoms. There is thus uncertainty as to whether the drugs might simply be masking the depression in a manner comparable to anxiety-relieving agents, and uncertainty whether patients should be regarded as temporarily dependent upon tricyclic drugs. Slow brain processes have to be inferred, of a duration often met in psychiatry (Oswald, 1967). The observations we now report have features in common with many other slow brain recovery processes Oswald, 1969) and may cast light upon the mode of action of antidepressant drugs, as well as providing further insight into the chemical mechanisms of sleep. The latter are currently believed to be governed in part by cerebral mono-amines, which the tricyclic drugs are thought to affect.

Type
Research Article
Copyright
Copyright © Royal College of Psychiatrists, 1969 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Allen, C., Kales, A., and Berger, R. J. (1968). ‘An analysis of the effect of glutethimide on REM density.’ Psychon. Sci., 12, 329–30.Google Scholar
Andersen, H., and Kristiansen, E. S. (1959). ‘Tofranil-treatment of endogenous depressions.’ Acta psychiat. neurol. Scand., 34, 387–97.Google Scholar
Baekeland, F. (1967). ‘Pentobarbital and dextroamphetamine sulfate: effects on the sleep cycle in man’. Psychopharmacologia (Berl.), 11, 388–96.Google Scholar
Bergamasco, R., Brignolio, F., Doriguzzi, T., Fiore, P., Gentile, G., and Riccio, A., (1968). ‘Studio poligrafico longitudinale del sonno in 11 pazienti affetti da delirium tremens. Acta neurol., 23, 289–99.Google Scholar
Berger, R. J., and Oswald, I. (1962). ‘Eye movements during active and passive dreams.’ Science, 137, 601.CrossRefGoogle ScholarPubMed
Callaway, E. (1950). ‘Slow wave phenomena in intensive electroshock.’ Electroenceph. clin. Neurophysiol., 2, 157–62.Google Scholar
Carlsson, A., Rosengren, E., Bertler, A., and Nilsson, J. (1957). ‘Effect of reserpine on the metabolism of catecholamines,’ in Psychotropic Drugs fed. Garattini and Ghetti). Amsterdam.Google Scholar
Cox, B. M., Ginsburg, M., and Osman, O. H. (1968). ‘Acute tolerance to narcotic analgesic drugs in rats.’ Brit. J. Pharmac. 33, 245–56.Google Scholar
Dement, W. C. (1960). ‘The effect of dream deprivation.’ Science, 131, 1705–7.Google Scholar
Dement, W. C. (1965). ‘Studies on the function of rapid eye movement (paradoxical) sleep in human subjects’ in Neurophysiologie des États de Sommeil (ed. Jouvet). Paris.Google Scholar
Dement, W. C. and Wolpert, E. A. (1958). ‘The relation of eye movements, body motility and external stimuli to dream content.’ J. exp. Psychol., 55, 543–53.Google Scholar
Elderton, W. P. (1938). Frequency Curves and Correlation. Cambridge.Google Scholar
Evans, J. I., and Lew's, S. A. (1968). ‘Drug withdrawal state.’ Arch. gen. Psychiat., 19, 631–4.Google Scholar
Evans, J. I., Lew's, S. A., Gibb, I. A. M., and Cheetham, M. (1968). ‘Sleep and barbiturates: some experiments and observations.’ Brit. med. J., 4, 291–3.Google Scholar
Greenberg, R., and Pearlman, C. (1967). ‘Delirium tremens and dreaming.’ Amer.J. Psychiat., 124, 133–42.Google Scholar
Gross, M. M., Goodenough, D., Tobin, M., Halpert, E., Lepore, D., Perlstein, A., Sirota, M., Dibianco, J., Fuller, R., and Kishner, I. (1966). ‘Sleep disturbance and hallucinations in the acute alcoholic psychoses.’ J. nerv. ment. Dis., 142, 493514.Google Scholar
Hartmann, E. (1968a). ‘The effect of four drugs on sleep patterns in man.’ Psychopharmacologia (Bed.), 12, 346–53.Google Scholar
Hartmann, E. (1968b). ‘Amitriptyline and imipramine: effects on human sleep.’ Psychophysiol., 5, 207.Google Scholar
Iverson, L. L. (1967). The Uptake and Storage of Noradrenaline in Sympathetic Nerves. Cambridge.Google Scholar
Jouvet, M. (1967). ‘Mechanisms of the states of sleep: a neuropharmacological approach.’ Res. Publ. Ass. nerv. ment. Dis., 45, 86126.Google Scholar
Kales, A., Hoedemaker, F. S. Jacobson, A. and Lichtenstein, E. D. (1964). ‘Dream deprivation: an experimental appraisal.’ Nature, 204, 1337–8.Google Scholar
Kales, A., Hoedemaker, F. S. Jacobson, A. and Jacobson, A. (1967). ‘Mental activity during sleep: recall studies, somnambulism, and effects of rapid eye movement deprivation and drugs’. Exp. Neurol. Suppl. 4, 81–9.Google Scholar
Kales, A., Hoedemaker, F. S., Kales, J. D., Marusak, C., and Hanley, J. (1968a). ‘Effects of drugs on sleep.’ Psychophysiol., 4, 391–2.Google Scholar
Kales, A., Malmstrom, E. J., Rickles, W. H., Hanley, J., Ling Tan, T., Stadel, B., and Hoedemaker, F. S. (1968b). ‘Sleep patterns of a pentobarbital addict: before and after withdrawal.’ Psychophysiol., 5, 208.Google Scholar
Karacan, E., Goodenough, D. R., Shapiro, A., and Starker, S. (1966). ‘Erection cycle during sleep in relation to dream anxiety.’ Arch. gen. Psychiat., 15, 183–9.Google Scholar
Kramer, J. C, Klein, D. F., and Fink, M. (1961). ‘Withdrawal symptoms following discontinuation of imipramine therapy.’ Amer. J. Psychiat., 118, 549–50.Google Scholar
Le Gassicke, J., Ashcroft, G. W., Eccleston, D., Evans, J. I., Oswald, I., and Ritson, E. B. (1965). ‘The clinical state, sleep and a mine metabolism of a tranylcypromine (‘Parnate’) addict.’ Brit. J. Psychiat., 111, 357–64.Google Scholar
Lewis, S. A. (1968). ‘The quantification of rapid eye movement sleep’ in Drugs and Sensory Functions, Herxheimer, A. (ed.). London.Google Scholar
Lewis, S. A. Oswald, I., Evans, J. I., Akindele, M. O., and Tompsett, S. L. (1969). ‘Heroin and human sleep.’ Electroenceph. clin. Neurophysiol. (In Press).Google Scholar
Moody, J. P., Tait, A. C., and Todrick, A. (1967). ‘Plasma levels of imipramine and desmethylimi-pramine during therapy.’ Brit. J. Psychiat., 113, 183–93.Google Scholar
Oswald, I. (1967). ‘Slow neurophysiological swings’ Ann. N.T. Acad. Sci., 138, 616–22.Google Scholar
Oswald, I. (1968). ‘Drugs and sleep.’ Pharmac. Rev., 20, 274303.Google Scholar
Oswald, I. (1969). ‘Human brain protein, drugs and dreams. Nature, 223, 893–7.Google Scholar
Oswald, I., Berger, R. J., Jaramillo, R. A., Keddie, K. M. G., Olley, P. C., and Plunkett, G. B. (1963). ‘Melancholia and barbiturates: a controlled EEG, body and eye movement study of sleep.’ Brit. J. Psychiat., 109, 6678.CrossRefGoogle ScholarPubMed
Oswald, I., Evans, J. I., and Lewis, S. A. (1969). ‘Addictive drugs cause suppression of paradoxical sleep and withdrawal rebound’ in Scientific Basis of Drug Dependence (ed. Steinberg, ). London.Google Scholar
Oswald, I., Evans, J. I., and Priest, R. G. (1965). ‘Five weeks to escape the sleeping pill habit.’ Brit. med. J., 2, 1093–5.Google Scholar
Oswald, I., Evans, J. I., and Thacore, V. R. (1963). ‘Amphetamine and phenmetrazine addiction: physiological abnormalities in the abstinence syndrome.’ Brit. med. J., 2, 427–31.Google Scholar
Pivik, R., and Foulkes, D. (1966). ‘Dream deprivation’: effects on dream content.’ Science, 153, 1282–4.Google Scholar
Rechtschaffen, A., Kales, A., Berger, R. J., Dement, W. C., Jacobson, A., Johnson, L. C, Jouvet, M., Monroe, L. J., Oswald, I., Roffwarg, H. P., Roth, B., and Walter, R. D. (1968). A Manual of Standardized Terminology, Techniques and Scoring System for Sleep Stages of Human Subjects. Washington, D.C. Google Scholar
Roth, M. (1951). ‘Changes in the EEG under barbiturate anaesthesia produced by electroconvulsive treatment and their significance for the theory of ECT action.’ Electroenceph. clin Neurophysiol., 3, 261–80.Google Scholar
Schildkraut, J. J., and Kety, S. S. (1967). ‘Biogenic amines and emotions.’ Science, 156, 2130.Google Scholar
Toyoda, J. (1964). ‘The effects of chlorpromazine and imipramine on the human nocturnal sleep electroencephalogram.’ Folia psychiat. neur. Jap., 18, 198221.Google Scholar
Way, E. L., Loh, H. H., and Shen, F. H. (1968). ‘Morphine tolerance, physical dependence, and synthesis of brain 5-hydroxytryptamine.’ Science, 162, 1290–2.Google Scholar
Williams, R. L., Agnew, H. W., and Webb, W. B. (1966). ‘Sleep patterns in the young adult female: an EEG study.’ Electroenceph. clin. Neurophysiol., 20, 264–6.Google Scholar
Submit a response

eLetters

No eLetters have been published for this article.