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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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BackgroundSubthreshold bipolarity: diagnostic issues and challenges
Nusslock, R., & Frank, E. (2011) · Bipolar Disorders · doi:10.1111/j.1399-5618.2011.00957.x · Cited by 112
“(121) first described an association between antidepressant use and a new or worsening rapid-cycling course of illness in those with bipolar disorder.”
Hoertel, N., Strat, Y. L., Angst, J., & Dubertret, C. (2012) · Journal of Affective Disorders · doi:10.1016/j.jad.2012.09.016 · Cited by 106
“53%) of individuals with D(m) than that documented in prior studies (Akiskal and Mallya, 1987; Angst, 2006; Angst et al., 2003, 2010; Benazzi, 1997a, 1997b, 2007; Hantouche et al., 1998; Kukopulos et al., 1980; Manning et al., 1997; Zimmermann et al., 2009).”
BackgroundResultTREATMENT-RESISTANT BIPOLAR DEPRESSION
Sachs, G. S. (1996) · Psychiatric Clinics of North America · doi:10.1016/s0193-953x(05)70285-9 · Cited by 107
Possible role of antidepressants in precipitating mania and hypomania in recurrent depression
Kupfer, D. J., Carpenter, L. L., & Frank, E. (1988) · American Journal of Psychiatry · doi:10.1176/ajp.145.7.804 · Cited by 105
Post, R. M., Altshuler, L. L., Frye, M. A., Suppes, T. M., Rush, A. J., Keck, P. E., McElroy, S. L., Denicoff, K. D., Leverich, G. S., Kupka, R., et al. (2001) · Bipolar Disorders · doi:10.1034/j.1399-5618.2001.030505.x · Cited by 133
Antidepressant-induced sexual dysfunction.
Segraves, R. T. (1998) · PubMed · Cited by 103
Gender differences in the phenomenology of bipolar disorder
Kessing, L. V. (2004) · Bipolar Disorders · doi:10.1111/j.1399-5618.2004.00135.x · Cited by 98
Post, R. M., & Weiss, S. R. B. (1996) · Molecular Neurobiology · doi:10.1007/bf02740751 · Cited by 99
Bipolar Mood Disorder: Practical Strategies for Acute and Maintenance Phase Treatment
SACHS, G. S. (1996) · Journal of Clinical Psychopharmacology · doi:10.1097/00004714-199604001-00005 · Cited by 97
Long-Term Olanzapine Therapy in the Treatment of Bipolar I Disorder
Sanger, T. M., Grundy, S. L., Gibson, P. J., Namjoshi, M. A., Greaney, M. G., & Tohen, M. F. (2001) · The Journal of Clinical Psychiatry · doi:10.4088/jcp.v62n0410 · Cited by 99
The phenotypes of bipolar disorder: relevance for genetic investigations
MacQUEEN, G. M., Hájek, T., & Alda, M. (2005) · Molecular Psychiatry · doi:10.1038/sj.mp.4001701 · Cited by 99
Current research on rapid cycling bipolar disorder and its treatment
Calabrese, J. R., Shelton, M. D., RAPPORT, D. J., Kujawa, M. J., Kimmel, S. E., & Caban, S. (2001) · Journal of Affective Disorders · doi:10.1016/s0165-0327(98)00161-x · Cited by 100
Predictors of Response to Mood Stabilizers
CALABRESE, J. R., FATEMI, S. H., KUJAWA, M., & WOYSHVILLE, M. J. (1996) · Journal of Clinical Psychopharmacology · doi:10.1097/00004714-199604001-00004 · Cited by 95
Rational Use of Antidepressant Drugs
Fava, G. A. (2014) · Psychotherapy and Psychosomatics · doi:10.1159/000362803 · Cited by 95
McCarthy, M. J., Nievergelt, C. M., Shekhtman, T., Kripke, D. F., Welsh, D. K., & Kelsoe, J. R. (2011) · Genes Brain & Behavior · doi:10.1111/j.1601-183x.2011.00725.x · Cited by 94
“For example, euphoric mania and a positive family history are considered to be the factors favoring Li response, whereas dysphoric mania, the presence of comorbid psychiatric conditions and a negative family history are considered poor prognostic indicators (Kukopulos et al. 1980, Grof et al. 2003).”
BackgroundSpecial considerations in treating bipolar disorder in women
Burt, V. K., & Rasgon, N. (2004) · Bipolar Disorders · doi:10.1046/j.1399-5618.2003.00089.x · Cited by 94
Pharmacological Management of Bipolar Depression: Acute Treatment, Maintenance, and Prophylaxis
Vieta, E., & Valentí, M. (2013) · CNS Drugs · doi:10.1007/s40263-013-0073-y · Cited by 96
“First-generation antipsychotics were not effective in the prevention of depressive episodes, and could even cause them [140].”
BackgroundDuration and stability of the rapid-cycling course: a long-term personal follow-up of 109 patients
Koukopoulos, A. E., Sani, G., Koukopoulos, A. E., Minnai, G. P., Girardi, P., Pani, L., Albert, M. J., & Reginaldi, D. (2002) · Journal of Affective Disorders · doi:10.1016/s0165-0327(02)00321-x · Cited by 95
Self-citationResponse to lithium maintenance treatment in bipolar disorders: comparison of women and men
Viguera, A. C., Baldessarini, R. J., & Tondo, L. (2001) · Bipolar Disorders · doi:10.1034/j.1399-5618.2001.30503.x · Cited by 92
Self-citationRapid cycling bipolar disorder – diagnostic concepts
Bauer, M., Beaulieu, S., Dünner, D. L., Lafer, B., & Kupka, R. (2008) · Bipolar Disorders · doi:10.1111/j.1399-5618.2007.00560.x · Cited by 91
“(56) noted that antidepressant use caused acceleration in the cycle frequency from 0.”
BackgroundInfluentialMixed depressive states: Nosologic and therapeutic issues
Koukopoulos, A., Albert, M. J., Sani, G., Koukopoulos, A. E., & Girardi, P. (2005) · International Review of Psychiatry · doi:10.1080/09540260500064744 · Cited by 89
“We hold that it is no coincidence that 28% of bipolar patients present the same cycle pattern consisting of mania followed by depression, which in most cases is of a simple or clearly inhibited type (Kukopulos et al., 1980).”
BackgroundRapid cycling depression in adolescence
Spurkland, I., & Vandvik, I. H. (1989) · Acta Psychiatrica Scandinavica · doi:10.1111/j.1600-0447.1989.tb01300.x · Cited by 89
The bipolar spectrum: Conceptions and misconceptions
Ghaemi, S. N., & Dalley, S. (2014) · Australian & New Zealand Journal of Psychiatry · doi:10.1177/0004867413504830 · Cited by 90
“In particular, he cast doubt on the treatment response criterion: many unipolar patients did not respond to antidepressants; they seemed to have other features of bipolarity, such as a highly recurrent course and early age of onset (Kukopulos et al., 1980).”
BackgroundPost, R. M., Denicoff, K. D., Frye, M. A., Dunn, R. T., Leverich, G. S., Osuch, E. A., & Speer, A. (1998) · Neuropsychobiology · doi:10.1159/000026532 · Cited by 87
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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