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Cited by 73Bipolar Disorder and TreatmentTreatment of Major DepressionNeuroscience and Neuropharmacology Research

Antidepressant withdrawal-induced activation (hypomania and mania): Mechanism and theoretical significance

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Dilsaver, Steven C., Greden, John F.·1984·Brain Research Reviews
DOI 10.1016/0165-0173(84)90028-6
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Abstract

Electrocortical and behavioral arousal are separate phenomena subserved by different neural substrata operating in parallel. A comprehensive theory of 'activation' must take into account the relationships between the electrical and behavioral activating systems. In pathological or experimentally induced states paradoxes, resolvable by a theory positing functional interaction between these systems, arise. EEG arousal is directly mediated, in both the waking and sleeping state, by cholinergic mechanisms. Antidepressant withdrawal precipitates cholinergic overdrive; this would account for the apparent disturbances of REM sleep occurring when antidepressants are stopped. Generally, cholinergic overdrive would produce behavioral inhibition but in particular instances it triggers marked psychomotor arousal by mobilizing a 'limbic activating system'. The existence of a monoaminergic 'limbic activating system', system 'A', with the properties attributed to it in this paper, is supported by both clinical and laboratory observations. System 'A' theory provides a parsimonious means of adequately explaining many phenomena. This theory also has in its favor explanatory power and scope. The Cholinergic-Monoaminergic Interaction Theory of antidepressant withdrawal induced activation and of rapidly-cycling manic-depressive illness maintains that system 'A' and a cholinergic inhibitory system interact dynamically, and that excessive monoaminergic function can precipitate excessive cholinergic function and a dearth of monoaminergic function (due to autoregulation) and hence depression. Likewise, excessive cholinergic function is posited to activate monoaminergic systems and hence to secondarily cause behavioral activation. Rapidly-cycling manic-depressive patients, according to the model, develop alternating cholinergic and monoaminergic overdrive states because the homeostatic mechanisms which should serve to maintain, within normal limits, the composite of cholinergic inhibitory and monoaminergic activating influences are defective. Consequently, rather than reaching a reasonable balance compatible with adaptive function there is oscillation between extremes. Each oscillatory movement is actually a move towards the 'golden mean' and is induced by deviation from this ideal but the defective homeostatic mechanisms promote ' perpetual ' overshooting. Lithium and ECT may be useful in the treatment of rapidly-cycling patients as both treatments may down-regulate muscarinic receptors, and otherwise modify cholinergic and monoaminergic systems in ways promoting homeostasis.(ABSTRACT TRUNCATED AT 400 WORDS)

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  • Substituting diazepam with lorazepam has shown little evidence to support its efficacy.

    “Some authors suggested tapering from other BZDs such as lorazepam after substituting diazepam [79], according to Murphy and Tyrer [80] such substitution has shown little evidence to support its efficacy.”

    From Acute and Persistent Withdrawal Syndromes Following Discontinuation of Psychotropic Medications (2020) · cites this paper as [79]

    The passages from §3.5 concern antidepressant-withdrawal activation and include references to benzodiazepine receptors, but do not discuss substituting diazepam with lorazepam or whether that substitution is effective. Searches for the drugs and for Murphy and Tyrer found no passage addressing the claim; page numbers were unavailable in our copy. (LLM, conf=0.76)

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5 of the 207 references couldn’t be matched to a known paper.

Research works printed but not linked: 6

  1. Dilsaver, S. C.. Leckrone, J. G. and Greden, J. F.. An 'anticholinesterase-like' syndrome precipitated by psy- chotropic withdrawal in a chronic abuser of marijuana, Psychosomatics, in press.
  2. Dilsaver, S. C. and Greden. J. F., Antidepressant with- drawal phenomena: a review. Biol. Psychiarry, 19 (1984) 237-256.
  3. Klaassen. C. D., Principles of toxicology. In A. G. Gil- man, L. S. Goodman and A. Gilman, (Ed%), The Phar- macological Basis of Therapeutics, 6th edn., Edition Mac- millan, New York, 1980, pp. 1608. 111
  4. Lindsley, D. B. In J. Field (Ed.), Handbook of Physiolo- gy, Sect. 1,3, 1553, (American Physiology Society, Wash- ington D. C., 1960). 118
  5. Weiner, N., Norepinephrine, epinephrine and the sympa- thomimetic amines. In A. G. Gilman L. S. Goodman and A. Gilman (Eds.), The Pharmacological Basis of Thera- peutics, 6th edn., MacMillan, New York, 1980,161 pp. 199
  6. Westfall, T. C., Effect of acetylcholine on the release of ~H3]norepineph~ne by nicotine and potassium chloride from rat brain slices. In E. Usdin and S. H. Snyder (Eds.), Frontiers of Catecholamine Research, Pergamon Press, New York, 1973,617-618 pp. 201

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Authors
Dilsaver, S. C., & Greden, J. F.
Affiliations
  • Michigan Medicine (US)
  • University of Michigan (US)
Corresponding author
Dilsaver, Steven C.
Venue
Brain Research Reviews
Publisher
Elsevier BV
Published
1984-03
Volume
7
Issue
1
Pages
29-48
ISSN
0165-0173 (ISSN-L)
DOI
10.1016/0165-0173(84)90028-6
OpenAlex
W2417584883
Cited by
73
References
207
Citations by year
2021: 1 · 2020: 1 · 2019: 2 · 2018: 1 · 2015: 2 · 2014: 1 · 2013: 1 · 2012: 1
FWCI
2.08
Type
journal article
Language
en
Open access
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Brain Research Reviews (publishedVersion)
  • PubMed (publishedVersion)
  • Deep Blue (University of Michigan) (submittedVersion)
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Bipolar Disorder and Treatment
  • Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords
antidepressant discontinuation, hypomania, mania, behavioral arousal, EEG arousal, muscarinic receptors, lithium, electroconvulsive therapy, homeostatic mechanisms, depression, bipolar disorder
MeSH terms
Adrenergic Fibers, Animals, Antidepressive Agents, Arousal, Behavior, Animal, Bipolar Disorder, Brain, Cholinergic Fibers, Electroencephalography, Evoked Potentials, Humans, Sleep Stages, Substance Withdrawal Syndrome, Receptors, Neurotransmitter, Neurotransmitter Agents

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