Expert: Ivan Goldberg, M.D. - 12/2/2005

Question
Hello again and thankyou for the reply.  We are up in Canada, so your list won't quite help us.  But, the doctor she has seems to be quite good, according to many others and according to my intuition etc.
If a combo of lithium/olanzypine/cyprexa doesn't seem to be working after a month, do you think uping the olanzepine will work?  How about trying another mood-stabilizer?  Any suggestions?  Thankyou for your kindness in helping people this way.
-------------------------
Followup To
Question -
Hello,
I have been having the most horrible time trying to help get my wife (28yrs old) stabilzed.  We have a young baby and soon after, post-partum turned to phycosis and 3 weeks in the hospital.  Following this, she was put on Olanzapine and Cyprexa, and was thought to be recovering from post-partum phycosis.  
In the past five months she has swung from depression to 'mania about ten times.  I have had a horrible time convincing her phyciatrist of the 'hypo-manic' episodes as she does a great job of coming off as though she is 'fine' when she sees him.  She has also painted me as controlling and laughed off my concerns. About a month ago she was finally labeled Bipolar. (Her father is also and has never gotten it under control due to alcoholism and failure to stick to meds) After so many months of heart-wrenching swinging, with her GP's help, we finally got her Phyciatrist to put her on Lithium,(one month ago today) Her blood tests show that she is at 0.6 (i think this is right, just above the lowest common dosage)for the Lithium but, STILL she has shot up like usual and our lives are HELL, especially mine and our baby son as i cannot trust her at all during the hypo-mania.  
CAN YOU HELP?  I am feeling so sad, desperate.  Losing hope and strength to hold our little family together.  She is normally a sweet woman, kind and fun.  She is well educated, has a degree, very successful in her field but now...  Now she is 'up' and mean, and wreckless.  She stole something from a store yesterday!! I was shocked!  She lies with such astounding ability.   
Is it likely the anti-depresant Cyprexa is exasperating or causing the rapid-cycling?  Now her doc has talked about increasing the Olanzipine to where it was in the beginning (they lowered it a couple months ago)but, i am not holding my breath.  it didn't work before, but perhaps in combo with the lithium?  Oh, this is such a frightening strugggle.  Is there hope, what can i do?
Answer -
Scott . . .

Rapidly-cycling bipolar disorder is difficult for the family and for the doctors treating it. it also can be very difficulty for the patient.

Lithium, Depakote, olanzapine, Tegretol, other mood stabilizers and other antipsychotic drugs havers all helped some people. so have novel treatments such as high-dose thyroid and nimodipine.

I think he most important thing is that your wife be treated by a psychiatrist who has a good deal of experience working with people who have  hard-to-treat mood disorders. A list of such psychiatrists may be found at:
http://www.psycom.net/depression.central.psychiatrists.html

Best regards . . .

Ivan
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Answer
Scott . . .

Below are a few abstracts that may give you, and possibly your wife's doctor, some ideas as to what can be done.

Best regards . . .

Ivan
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1: CNS Drugs. 2005;19(7):557-69.

Rapid cycling bipolar disorder: clinical characteristics and treatment options.

Coryell W.

Psychiatry Research Department, University of Iowa, Carver College of Medicine,
Iowa City, Iowa 52242, USA. william-coryell@uiowa.edu

Approximately one of six patients who seek treatment for bipolar disorder
present with a rapid cycling pattern. In comparison with other patients who have
bipolar disorder, these individuals experience more affective morbidity in both
the immediate and distant future and are more likely to experience recurrences
despite treatment with lithium or anticonvulsants. Particular care should be
given to distinguishing rapid cycling bipolar disorder from attention-deficit
hyperactivity disorder in children or adolescents and from borderline
personality disorder in adults. Perhaps four of five cases of rapid cycling
resolve within a year, but the pattern may persist for many years in the
remaining patients. As with bipolar disorder in general, depressive symptoms
produce the most morbidity over time. Controlled studies have not established
that antidepressants provoke switching or rapid cycling, but neither have they
been shown consistently to have benefits in bipolar illness. Successful
management will often require a sequence of trials with mood stabilizer drugs,
beginning with lithium in treatment-naive patients. Efforts to minimise adverse
effects, and the recognition that full benefits may not be apparent for several
months, will make the premature abandonment of a potentially helpful treatment
less likely. Placebo-controlled studies so far provide the most support for the
use of lithium and lamotrigine as prophylactic agents. The combination of
lithium and carbamazepine, valproate or lamotrigine for maintenance has some
support from controlled studies, as does the adjunctive use of olanzapine.

Publication Types:
   Review

PMID: 15984894 [PubMed - indexed for MEDLINE]

2: Acta Psychiatr Scand. 2003 Jul;108(1):4-14.

Comment in:
   Acta Psychiatr Scand. 2003 Jul;108(1):1-3.

Rapid-cycling bipolar disorder: effects of long-term treatments.

Tondo L, Hennen J, Baldessarini RJ.

Department of Psychiatry and Neuroscience Program, Harvard Medical School, USA.

OBJECTIVE: To compare responses to long-term treatment of rapid-cycling (RC) vs.
non-RC bipolar disorder patients and assess relative effectiveness of specific
agents in RC patients. METHOD: Studies identified by literature searching were
analyzed for effects of RC status and treatment-type on clinical outcome
(recurrence or non-improvement per exposure-time), using random-effects methods
to estimate pooled rates and their 95% CI for quantitative meta-analytic
modeling. RESULTS: Data were obtained from 16 reports with 25 trial-arms
involving 1856 (905 RC and 951 non-RC) patients treated with carbamazepine,
lamotrigine, lithium, topiramate, or valproate, alone or with other agents over
an average of 47.5 months (7347 total patient-years). Estimated RC prevalence
was 15.4%. Crude rates (%/month) of recurrence (2.31/1.20) and clinical
non-improvement (1.93/0.49) averaged 2.9-fold greater in RC vs. non-RC subjects.
The pooled RC/non-RC risk ratio (RR) for inferior treatment-response (in 13
direct comparisons) was 1.40 (CI 1.26-1.56; P < 0.0001). Pooled crude recurrence
and non-improvement rates suggested no clear advantage for any treatment, nor
superiority for anticonvulsants over lithium. However, only lithium vs.
carbamazepine could be directly compared (in four treatment-arms)
meta-analytically in RC patients (RR = 0.93, CI 0.74-1.18, indicating no
difference in effectiveness). CONCLUSION: As expected, RC was associated with
lower effectiveness of all treatments evaluated. Direct comparisons of specific
treatment alternatives for RC patients were rare, and provided no secure
evidence of superiority of any treatment. Additional long-term studies comparing
RC/non-RC patients randomized to specific treatments are required.

Publication Types:
   Review
   Review, Tutorial

PMID: 12807371 [PubMed - indexed for MEDLINE]

3: J Affect Disord. 2002 Dec;72 Suppl 1:S15-21.

Relevance of new and newly rediscovered anticonvulsants for atypical forms of
bipolar disorder.

Grunze H, Walden J.

Department of Psychiatry, LMU, Nussbaumstr. 7, D-80336 Munich, Germany.
grunze@psy.med.uni-muenchen.de

The so-called atypical forms of bipolar disorder are not a rarity, but instead
are rather the rule. Particularly in specialized settings such as the bipolar
disorder clinic, the majority of patients are characterized by atypical
manifestations (). Mixed states, psychotic mania and a rapid cycling course of
bipolar disorder are a challenge both to pharmacological and non-pharmacological
treatment. The benefit of classical mood stabilizers such as lithium and
carbamazepine is limited in monotherapy, although valproate has a broader
spectrum of activity in atypical bipolar disorders and is often used in
combination with other agents. Thus, new treatment alternatives are needed
urgently for optimizing the treatment of atypical bipolar disorder. During the
last decade, several new antiepileptic drugs have been released, e.g.
lamotrigine, gabapentin, tiagabine, topiramate and levetiracetam. Others have
been available for some time, but only recently have become the focus of bipolar
disorder research; for example, phenytoin, and especially, oxcarbazepine. This
review will consider our current knowledge of the benefit of these new and newly
rediscovered anticonvulsants in treating bipolar disorders, with a special focus
on their value in treating atypical manifestations.

Publication Types:
   Review
   Review, Tutorial

PMID: 12589899 [PubMed - indexed for MEDLINE]

4: Curr Psychiatry Rep. 2001 Dec;3(6):451-62.

Rapid cycling bipolar disease: new concepts and treatments.

Dubovsky SL.

Department of Psychiatry, University of Colorado School of Medicine, 4200 East
9th Avenue, Denver, CO 80262, USA. Steven.Dubovsky@UCHSC.edu

Having been recognized by Kraeplin at the beginning of the 20th century, rapid
cycling was first described as a specific entity by Dunner et al. in 1974. The
prevalence of rapid cycling ranges from 12% to 20% in patients with bipolar
disorder who are not selected for a high rate of cycling.

Publication Types:
   Review

PMID: 11707158 [PubMed - indexed for MEDLINE]

5: Expert Opin Pharmacother. 2001 Dec;2(12):1963-73.

Rapid cycling bipolar disorder.

Barrios C, Chaudhry TA, Goodnick PJ.

Department of Psychiatry & Behavioural Sciences, University of Miami School of
Medicine, D79, 1400 NW 10 Avenue, Ste 304A, Miami, FL 33136, USA.

Rapid cycling bipolar disorder (RCBD) is defined in the fourth edition of the
Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) as a type of
manic-depressive illness in which the patient experiences four or more episodes
of mania and/or major depression per year. It was first reported as a
consequence of the reduced effectiveness of lithium carbonate in the treatment
and prophylaxis of this form of bipolar disorder (BD) in contrast to those with
less frequent cycling. Among the anticonvulsants, there have been reports with
different degrees of controlled data concerning carbamazepine, valproate,
lamotrigine, topiramate, gabapentin and primidone. There is a paucity of
double-blind studies, but what is available supports the use of lamotrigine.
There is open data supporting the use of carbamazepine, valproate and
topiramate. Regarding other classes, nimodipine may have specific utility in
ultradian- (ultra-ultra-) or ultra-RCBD and there is double-blind data regarding
the specific utility of olanzapine in RCBD. Low thyroid function may be a factor
in development of RCBD; therapies aimed at elevating thyroid levels, even beyond
the usual range, have frequently produced benefits in open trials. More research
is needed into the possible therapeutic benefits of verapamil, bupropion,
choline, light therapy and electroconvulsive therapy (ECT).

Publication Types:
   Review
   Review, Tutorial

PMID: 11825328 [PubMed - indexed for MEDLINE]

6: Bipolar Disord. 2000 Dec;2(4):305-15.

Emerging trends in the treatment of rapid cycling bipolar disorder: a selected
review.

Post RM, Frye MA, Denicoff KD, Leverich GS, Dunn RT, Osuch EA, Speer AM, Obrocea
G, Jajodia K.

Biological Psychiatry Branch, National Institute of Mental Health, NIH,
Bethesda, MD 20892-1272, USA.

Recent evidence suggests that lithium therapy (even as supplemented by
antidepressants and neuroleptics) is inadequate for the majority of patients
with bipolar illness, and particularly those with rapid cycling. Valproate and
carbamazepine have emerged as adjuncts and alternatives, but they, too, often
require additional approaches with lithium, thyroid hormones, and other putative
mood stabilizers, including nimodipine (and related dihydropyridine calcium
channel blockers), lamotrigine, gabapentin, topiramate, and the atypical
neuroleptics. Evaluating how these agents and the unimodal antidepressants are
optimally applied and sequenced in the treatment of bipolar illness with its
multiple subtypes, patterns and comorbidities will require much future
investigation and the development of new methodological clinical trial
approaches.

Publication Types:
   Review
   Review, Tutorial

PMID: 11252642 [PubMed - indexed for MEDLINE]

7: Bipolar Disord. 2000 Sep;2(3 Pt 1):165-73.

The use of nimodipine in the treatment of mood disorders.

Goodnick PJ.

Department of Psychiatry and Behavioral Sciences, University of Miami School of
Medicine, FL 33136, USA. pgoodnick@aol.com

Nimodipine, a dihydropyridine calcium entry blocker, has been shown to protect
from neuronal damage due to ischemia by providing for increased postischemic
perfusion. Further, it has also been demonstrated to have antiepileptic
properties. These two properties--calcium channel blockade and anticonvulsant
benefits have been applied with success to mood disorder treatment. Although
found helpful nearly a decade ago for uncomplicated mania, nimodipine may have
particular benefits for those diagnostic subclasses of bipolar disorder most
resistant to therapy, e.g., ultra-rapid-cycling bipolars and brief recurrent
depressions.

Publication Types:
   News

PMID: 11256683 [PubMed - indexed for MEDLINE]

8: Psychiatry Clin Neurosci. 1999 Oct;53 Suppl:S73-5.

Algorithm for the treatment of rapid cycling.

Yamada K.

Department of Psychiatry, Urafune Hospital of Yokohama City University School of
Medicine, Yokohama, Japan.

Rapid cycling is a clinical subtype of bipolar mood disorder that has four or
more episodes during the previous 12 months and has poor response to lithium
(Li) prophylaxis treatment. Therefore it is said the refractory mood disorder
and algorithm for treatment of rapid cycling is to be expected. The first choice
of drug for rapid cycling is Li, the second choice is carbamazepine (CBZ) or
valproic acid (VPA), in addition to Li, the third choice is clonazepam (CNZP) in
addition to Li, and CBZ or VPA, the fourth choice is levothyroxine or
bromocriptine in addition to them, and the fifth choice is electroconvulsive
therapy.

Publication Types:
   Review
   Review, Tutorial

PMID: 10560903 [PubMed - indexed for MEDLINE]

9: Psychiatr Clin North Am. 1999 Sep;22(3):585-607.

Rapid-cycling bipolar disorder. An overview of research and clinical experience.

Kilzieh N, Akiskal HS.

VA Puget Sound Health Care Services, Tacoma, Washington, USA.

Although many studies of RCBD have been reported over the last 2 decades,
knowledge remains limited. Higher incidence in women is the sole clearly
replicated finding in most studies. This finding might be mediated by
cyclothymia, a temperament that is of higher prevalence in women and that might
be considered as a normal variant of RC. Many questions remain unanswered.
Review of putative risk factors, such as hypothyroidism and treatment with
antidepressants, provides no conclusive answers. There is clinical evidence to
implicate both factors. In principle, the thyroid connection can be approached
rationally, yet there seems to be no relationship between thyroid status and
response to thyroid augmentation. For this reason and given the potential risks
of long-term thyroid use, this strategy should not be the first one to be tried
in RC. Cumulatively, naturalistic studies over the past 30 years have strongly
implicated antidepressants in switching and cycle acceleration, yet the
double-blind, controlled, prospective studies that are needed to provide
definitive answers are unlikely to be conducted for ethical reasons discussed in
this article. Bipolar family history of RC probands appears indistinguishable
from non-RC probands, indicating that most likely RCBD does not breed true.
Although RC seems to be more lithium resistant with less likelihood of being
symptom-free after 2 to 5 years of follow-up, many of these patients nonetheless
have resolution of the RC course. There is no marked difference in suicide
rates. An association of RC with bipolar type II, D-M-I pattern and those who
switch into mania or hypomania on antidepressants is a provocative possibility:
Antidepressants might introduce RC by first inducing a switch during a
depressive episode, creating a D-M-I pattern, a pattern that is poorly
responsive to lithium, which eventually degenerates into RC. Again, this
sequence might be mediated by the high prevalence of cyclothymia in bipolar II
patients. Thus, data from phenomenology, family history, and long-term outcome
do not support RC as a separate entity. RC appears to be a temporary complicated
phase in the illness, not a stable feature. This was noted by Kraepelin: I think
I am convinced that that kind of classification must of necessity wreck on the
irregularity of the disease. The kind and duration of the attacks and the
intervals by no means remain the same in the individual case but may frequently
change, so that the case must be reckoned always to new forms. Data by
Gottschalk et al testify to the chaotic mood swings of contemporary bipolar
disorder. Moreover RC is seen in other medical diseases, such as epilepsy, in
which patients have phases of increase in frequency of episodes (seizures) that
become refractory to treatment. Further longitudinal prospective studies are
required to understand the complexity of this intriguing phenomenon and to
provide better treatments. Algorithms deriving from tertiary research or
university-based clinical experience may not generalize to RC or otherwise
treatment-resistant bipolar patients seen in more routine practice. Illness
severity in RCBD generally precludes double-blind controlled investigations.
Meanwhile, clinicians may rely on discontinuing antidepressants, maintaining
patients on combined mood stabilizers--of which valproate is probably the most
useful--and making judicious use of atypical neuroleptics. Benzodiazepines and
alcohol (which produce withdrawal), caffeine, stimulants, exposure to bright
light, and sleep deprivation during excited phases should be avoided. Thyroid
and nimodipine augmentation can be considered in those with the most malignant
course. These are patients who need the maximal support that their psychiatrist
can provide them. Office visits must be arranged as the last appointment of the
day.

Publication Types:
   Review
   Review, Tutorial

PMID: 10550857 [PubMed - indexed for MEDLINE]

10: J Child Adolesc Psychopharmacol. 1999;9(1):51-61.

Nimodipine treatment of an adolescent with ultradian cycling bipolar affective
illness.

Davanzo PA, Krah N, Kleiner J, McCracken J.

Department of Psychiatry and Behavioral Sciences, University of California, Los
Angeles, USA.

This is a single case report of an open trial of nimodipine, a
dihydropyridine-type calcium antagonist, in the treatment of a 13-year-old boy
with refractory, ultradian rapid cycling, bipolar disorder type I. Prior
clinical trials with calcium channel blockers in adults with ultrarapid cycling
affective disorder supported an empirical trial of nimodipine for treatment of
ultradian rapid cycling in this adolescent. Severity of mania and depression
were rated before and after nimodipine therapy. A marked decrease in rapid,
repeated, and significant mood changes was clinically observed and measured by
standardized scales after 9 days of nimodipine 180 mg daily. No adverse effects
were noticed. Remission persisted with continued treatment at 36-month
follow-up. Medication response was partially attributed to adjunctive therapy
with levothyroxine. Implications of treatment benefit are discussed in the
context of novel pharmacotherapies for refractory bipolar disorder. These
findings are preliminary and do not provide sufficient basis to recommend
nimodipine as the treatment of choice in adolescents with ultradian cycling
bipolar disorder, but suggest that controlled studies may be indicated.

Publication Types:
   Case Reports

PMID: 10357518 [PubMed - indexed for MEDLINE]

11: J Clin Psychopharmacol. 1998 Oct;18(5):404-13.

Nimodipine monotherapy and carbamazepine augmentation in patients with
refractory recurrent affective illness.

Pazzaglia PJ, Post RM, Ketter TA, Callahan AM, Marangell LB, Frye MA, George MS,
Kimbrell TA, Leverich GS, Cora-Locatelli G, Luckenbaugh D.

Biological Psychiatry Branch, National Institute of Mental Health, National
Institutes of Health, Bethesda, Maryland 20892-1272, USA.

Of 30 patients with treatment-refractory affective illness, 10 showed a moderate
to marked response to blind nimodipine monotherapy compared with placebo on the
Clinical Global Impressions Scale. Fourteen inadequately responsive patients (3
unipolar [UP], 11 bipolar [BP]) were treated with the blind addition of
carbamazepine. Carbamazepine augmentation of nimodipine converted four (29%) of
the partial responders to more robust responders. Patients who showed an
excellent response to the nimodipine-carbamazepine combination included
individual patients with patterns of rapid cycling, ultradian cycling, UP
recurrent brief depression, and one with BP type II depression. When verapamil
was blindly substituted for nimodipine, two BP patients failed to maintain
improvement but responded again to nimodipine and remained well with a blind
transition to another dihydropyridine L-type calcium channel blocker (CCB),
isradipine. Mechanistic implications of the response to the dihydropyridine
L-type CCB nimodipine alone and in combination with carbamazepine are discussed.

Publication Types:
   Clinical Trial
   Randomized Controlled Trial

PMID: 9790159 [PubMed - indexed for MEDLINE]

12: Can J Psychiatry. 1997 Aug;42 Suppl 2:79S-86S.

Treatment of mania, mixed state, and rapid cycling.

Kusumakar V, Yatham LN, Haslam DR, Parikh SV, Matte R, Silverstone PH, Sharma V.

Department of Psychiatry, Dalhousie University, Halifax, Nova Scotia.
vkusumakar@usa.net

OBJECTIVES: To summarize the quality of evidence for the efficacy of different
biological treatments in mania, mixed state, and rapid cycling and to propose
guidelines for treatment of these conditions. METHOD: Articles published on
treatment of acute mania, mixed states, and rapid cycling were reviewed and
rated for quality of evidence using Periodic Health Examination guidelines.
RESULTS: Lithium and divalproex sodium are effective in classical pure mania,
whereas divalproex sodium and carbamazepine are likely more effective in mixed
states. Divalproex sodium is likely more efficacious than carbamazepine and
lithium when the mania is part of a rapid-cycling course. Typical neuroleptics
are efficacious in acute mania, particularly in the presence of marked psychotic
symptoms. Atypical neuroleptics can be useful in refractory mania. Some
benzodiazepines do have antimanic effects, but they are increasingly being shown
to have usefulness as adjuncts to mood stabilizers or neuroleptics rather than
as primary antimanic agents. Electroconvulsive therapy (ECT) is an efficacious
and broad-spectrum treatment. CONCLUSIONS: Mania can present with or without
mood-congruent or mood-incongruent psychotic features and as part of a
rapid-cycling or nonrapid-cycling course. Mixed state is a common presentation
in an acutely manic patient. The accurate assessment of these issues can serve
as a guide in determining treatment options and choices.

Publication Types:
   Review
   Review, Tutorial

PMID: 9288440 [PubMed - indexed for MEDLINE]

13: Encephale. 1997 May-Jun;23(3):209-17.

[Administration of high dose levothyroxine in treatment of rapid cycling bipolar
disorders. Review of the literature and initial therapeutic application apropos
of 6 cases]

[Article in French]

Afflelou S, Auriacombe M, Cazenave M, Chartres JP, Tignol J.

Laboratoire de Psychiatrie de l'Universite Victor Segalen de Bordeaux II,
Hopital Charles-Perrens, Centre Carreire.

INTRODUCTION: Rapid cycling among bipolar disorders was characterized in 1974 by
Dunner and Fieve by at least 4 episodes per year, lithium resistance, female
predominance. The idea of using thyroid hormones is based on frequent coexisting
thyroid dysfunction. Thyroid hormones where first used in the forties, and more
recently (table I) in open label and blind trials (Stancer et Persad, 1982;
Bauer et Whybrow, 1990). OBJECTIVE: Open label study of levothyroxine in rapid
cycling bipolar disorder. MATERIAL AND METHODS: Six subjects (4 females and 2
males, mean age 45.5 years at onset of bipolar disorder) meeting DMS III-R
criteria for rapid cycling bipolar disorder were consecutively included in an
open label study of levothyroxine. Subject characteristics are presented in
table II. RESULTS: After almost two years follow-up results appear positive in
67% of cases (2 complete remissions, 2 partial remissions and 2 failures).
CONCLUSION: Our cases, with data reported in the literature, support the
potential efficacy of levothyroxine for treatment of rapid cycling bipolar
disorder patients. We suggest a protocol for the good application of this
potential new treatment (table III).

Publication Types:
   Case Reports
   Review
   Review, Tutorial

PMID: 9333552 [PubMed - indexed for MEDLINE]

14: Acta Med Austriaca. 1994;21(2):47-52.

The therapeutic use of triiodothyronine and high dose thyroxine in psychiatric
disorder.

Whybrow PC.

Department of Psychiatry, University of Pennsylvania, Philadelphia 19104.

An intimate association between disturbances of thyroid hormone homeostasis and
behavior has been recognized for a long time already: Hyper- and hypothyroidism
can induce disturbances of mood and intellectual function (in severe cases even
psychosis can be mimicked). Reciprocally many psychiatric disturbances, such as
major depression and manic depressive disease have associated with them
disturbances of peripheral thyroid hormone metabolism. Approximately 10% of
depressed persons seem to have subclinical hypothyroidism and another
approximately 35% have a blunted TSH response to TRH. The use of lithium clearly
increases these numbers. In some cases a positive correlation between elevated
T4 and the speed of response to antidepressant drugs has been reported. Patients
with manic depressive disease respond less well to treatment with lithium when
they have a so called "rapid cycling disorder" (defined as more than 4 episodes
of disturbed behavior a year). These patients were shown to have a comparably
high incidence (up to 50%) of mild subclinical hypothyroidism. In an open study
of 11 patients (10 females--9 of them premenopausal--1 male) with rapid cycling
disorder adjunctive treatment with TSH suppressive doses of T4 (T4 levels at
approximately 150% of normal) reduced the manic and depressive phases in both
amplitude and frequency and even led to remittance in some patients. T4
treatment was begun only after stable "therapeutic" blood levels of lithium
carbonate and/or anticonvulsants have been reached, since it has been shown that
T4 therapy alone can precipitate dysphoric manic like symptoms which require
treatment with neuroleptics. Careful evaluation of possible side effects like

osteoporosis revealed surprisingly an even higher bone density in treated
patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Publication Types:
   Review
   Review, Tutorial

PMID: 7998482 [PubMed - indexed for MEDLINE]

15: Psychiatry Res. 1993 Dec;49(3):257-72.

Preliminary controlled trial of nimodipine in ultra-rapid cycling affective
dysregulation.

Pazzaglia PJ, Post RM, Ketter TA, George MS, Marangell LB.

Biological Psychiatry Branch, National Institute of Mental Health, National
Institutes of Health, Bethesda, MD 20892.

We report the initial results of the first controlled double-blind trial of
nimodipine, a calcium channel antagonist, in the acute and prophylactic
treatment of patients with treatment-refractory affective dysregulation. Active
drug nimodipine (A) was substituted for placebo (B) in 12 patients. Patients
were studied in a B-A-B design, with 3 of the 12 patients rechallenged with
active drug in a B-A-B-A design (patients 9, 10, and 11). Five of the nine
patients who completed the drug trial responded. One of three patients suffering
from ultra-ultra-rapid (ultradian) cycling bipolar II disorder (patient 6)
showed an essentially complete response; the other two ultradian patients
(patients 4 and 9) showed evidence of a partial response on manic and depressive
oscillations, one of which was confirmed in a B-A-B-A design. Only one of five
less rapidly, but continuously cycling patients showed an excellent response
(patient 10), and this was confirmed in a B-A-B-A design. The one patient who
had recurrent brief depression (patient 11) showed a complete resolution of
severe depressive recurrences, with response re-confirmed in an extended
prophylactic trial with a B-A-B-A design. In the eight patients who completed
self-ratings, nimodipine was associated with a significant reduction in the
magnitude of mood fluctuations compared with the baseline placebo condition.
Further clinical study of nimodipine, a calcium channel blocker with a unique
profile of behavioral and anticonvulsant properties, appears warranted in
patients with treatment-refractory affective illness characterized by recurrent
brief depression and ultradian cycling.

Publication Types:
   Clinical Trial
   Randomized Controlled Trial

PMID: 8177920 [PubMed - indexed for MEDLINE]