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Course of the Manic-Depressive Cycle and Changes Caused by Treatments
Abstract
The course of 434 bipolar patients (256 women, 178 men) was studied longitudinally. The prevailing patterns of the manic-depressive cycles at the end of the observation time were: mania followed by depression (usually mild), 28%; depression followed by mania (usually hypomania), 25%; and continuous circular course, with long cycles, 19%, or with short (rapid) cycles, 20%. The cycles followed an irregular pattern in 8% of the patients. As to the intensity of the episodes, 52% of the patients had severe depressions and hypomanias; 26% had severe manias and mild depressions; and 22% had severe depressions and severe manias. No significant sex differences was found regarding the patterns of the cycles or the intensity of the episodes, except among the rapid cyclers, where women (61) outnumbered men (26). With time the course tended to change from monopolar to bipolar, and the frequency of recurrence increased. Concurrent treatments, especially antidepressants, contributed to these changes, while female sex, middle age and menopause, along with antidepressant drugs, contributed to the establishment of rapid cyclicity. The depression-hypomania course was the one which was most prone to rapid cyclicity. Response to lithium prophylaxis was good in the maniadepression-free interval course, in the continuous circular course with long cycles, and in the irregular course. It was less good in the depression-mania-free interval course, where it increased the frequency of recurrences, although these were shorter and milder. Response was very poor in the rapid cycling course. But rapid cyclers and patients with the depressionmania-free interval course responded well to lithium when antidepressant drugs were not administered during the depressions. Zusammenfassung Der Verlauf der manisch-depressiven Zyklen bei 434 Patienten (256 Frauen, 178 Männer) wurde longitudinal untersucht. Die am Ende der Beobachtungszeit überwiegenden Verlaufsarten der manisch-depressiven Zyklen waren: Manie mit nachfolgender Depression (meist mild), 28%; Depression mit nachfolgender Manie (meist Hypomanie), 25%; kontinuierlich zyklischer Verlauf mit langen Zyklen, 19%; oder mit kurzen (schnellen) Zyklen, 20%. 8% der Patienten hatten Zyklen mit unregelmäßiger Verlaufsart. Hinsichtlich der Intensität der Episoden wurden folgende Beobachtungen gemacht: 52% der Patienten hatten schwere Depressionen und Hypomanien: 26% hatten schwere Manien und leichte Depressionen; 22% hatten schwere Depressionen und schwere Manien. Bei den Verlaufsarten der Zyklen oder der Intensität der Episoden gab es keine signifikanten geschlechtsspezifischen Unterschiede, mit Ausnahme der Patienten mit schnellen Zyklen, bei denen die Frauen (61) zahlenmäßig stärker vertreten waren als die Männer (26). Mit der Zeit bestand eine Tendenz zur Veränderung von monopolar nach bipolar und zu einer Zunahme der Häufigkeit von Rezidiven. Gleichzeitig vorgenommene Behandlungen, insbesondere mit Antidepressiva, trugen zu solchen Veränderungen bei, während das Auftreten rascher Zyklen häufiger beobachtet wurde bei Frauen, bei Patienten mittleren Alters und in der Menopause sowie bei gleichzeitiger Verabreichung von Antidepressiva. Die durch die Aufeinanderfolge von Depression und Hypomanie gekennzeichnete Verlaufsart tendierte am meisten zur Verkürzung und schnellerem Wechsel. Während des Krankheitsverlaufs mit aufeinanderfolgender Manie, Depression und freiem Intervall sprachen die Patienten gut auf Lithiumprophylaxe an, ebenso bei kontinuierlicher Verlaufsart mit langen Zyklen und bei irregulärem Verlauf. Das Ansprechen der Patienten war weniger deutlich ausgeprägt bei der Verlaufsart mit aufeinanderfolgender Depression, Manie und freiem Intervall, bei der die Häufigkeit von Rezidiven erhöht war, obwohl diese kürzer und milder verliefen. Sehr gering war das Ansprechen bei der schnellen zyklischen Verlaufsform. Die Patienten mit schnellen Zyklen und solche mit der Verlaufsart Depression, Manie, Intervall sprachen jedoch gut auf Lithium an, wenn während der depressiven Phasen keine Antidepressiva verabreicht wurden.
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“In the early 1980s, Koukopulos et al. observed how treatment by AD may change course from unipolar to bipolar illness.”
From May antidepressant drugs worsen the conditions they are supposed to treat? The clinical foundations of the oppositional model of tolerance (2020) · cites this paper as [35]
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“As pointed out by several authors (Wehr and Goodwin,1979; Kukopulos et al., 1980; Tondo et al., 1981; Akiskal and Mallya, 1987), a significant minority of depressive episodes cycles rapidly with exposure to antidepressants: some of these ‘refractory depression’ worsen with antidepressants, improve with discontinuation…”
BackgroundSelf-citationComparative pharmacology of bipolar disorder and schizophrenia
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Post, R. M. (1982) · Psychological Medicine · doi:10.1017/s003329170004900x · Cited by 39
Acute and maintenance treatment of bipolar mania: the role of atypical antipsychotics
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Psychotic and Mood Disorders Associated with the Perimenopausal Period
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“[29] Women with onset of BAD after age 40 years are less likely to be of the bipolar II type as opposed to those with onset before age 40 years.”
BackgroundFrequency of Hospitalisations and Inpatient Care Costs of Manic Episodes
de Zélicourt, M., Dardennes, R. M., Verdoux, H., Gandhi, G., Khoshnood, B., Chomette, E., Papatheodorou, M.-L., Edgell, E. T., EVEN, C., & Fagnani, F. (2003) · PharmacoEconomics · doi:10.2165/00019053-200321150-00002 · Cited by 37
The expanding indications for clozapine.
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Novel treatments for bipolar disorder
Bowden, C. L. (2001) · Expert Opinion on Investigational Drugs · doi:10.1517/13543784.10.4.661 · Cited by 36
The antidepressant effects of risperidone and olanzapine in bipolar disorder.
McIntyre, R. S., Mancini, D. A., Srinivasan, J., McCann, S., Konarski, J. Z., & Kennedy, S. H. (2004) · PubMed · Cited by 35
Rapid Cycling Bipolar Disorder
Coryell, W. H. (2005) · CNS Drugs · doi:10.2165/00023210-200519070-00001 · Cited by 36
What is to be done? Controversies in the Diagnosis and Treatment of Manic-Depressive Illness
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“[35] There is continued debate about the role of antidepressants in the development of rapid cycling through cycle acceleration.”
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“BD patients could exhibit a DMI/MDI cycle (depression or mania followed by mania/depression and free-interval), or a continuous cycle, in which the interval is absent [41,43,44].”
BackgroundWOMEN'S MENTAL HEALTH IN PRIMARY CARE
FRANK, J. B., Weihs, K. L., Minerva, E., & Lieberman, D. Z. (1998) · Medical Clinics of North America · doi:10.1016/s0025-7125(05)70611-8 · Cited by 34
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“The induction of mania has been linked to virtually every antidepressant (Kukopulos et al., 1980; Wehr and Goodwin, 1987; Altshuler et al., 1995; Kupfer et al., 1988; Peet, 1994; Joffe et al., 2002; Himmelhoch et al., 1991), although there is wide variation in the rates reported.”
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Who Responds to Prophylactic Lithium Therapy?
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Metadata
- Authors
- Kukopulos, A., Reginaldi, D., Laddomada, P., Floris, G., Serra, G., & Tondo, L.
- Venue
- Pharmacopsychiatry
- Publisher
- Georg Thieme Verlag KG
- Published
- 2008-03-13
- Volume
- 13
- Issue
- 04
- Pages
- 156-167
- ISSN
- 0176-3679 (ISSN-L)
- 1439-0795
- OpenAlex
- W147127941
- Cited by
- 436
- References
- 0
- Citations by year
- 2025: 2 · 2024: 6 · 2023: 10 · 2022: 2 · 2021: 8 · 2020: 1 · 2019: 6 · 2018: 7 · 2017: 3 · 2016: 12 · 2015: 10 · 2014: 10 · 2013: 10 · 2012: 9
- FWCI
- 10.77
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Pharmacopsychiatry (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Bipolar Disorder and Treatment
- Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Keywords
- bipolar disorder, rapid cycling, hypomania, depression, lithium prophylaxis, antidepressants, sex differences, menopause, recurrence, clinical course, treatment response, longitudinal follow-up, episode severity, age of onset, family history of bipolar disorder, comorbid depression
- MeSH terms
- Adolescent, Adult, Age Factors, Aged, Antidepressive Agents, Bipolar Disorder, Electroconvulsive Therapy, Female, Humans, Lithium, Longitudinal Studies, Male, Middle Aged, Sex Factors, Time Factors, Antipsychotic Agents
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