Bipolar Disorder Research
(The
Below Bipolar Disorder Research Comes From Bipolar Network News
& Various Other Resources)
Last
Five Years of Research Summarized
Demographic and clinical characteristics of individuals in a bipolar disorder case registry.
Genetics
378
genetic markers were examined and a linkage was found "between
bipolar illness vulnerability and loci on chromosomes 15q14 and
7q11.
Lithium
Lithium:
The literature was reviewed of patients taking lithium long term
to patients that discontinued it. "Suicidal acts rose 22-fold,
and fatalities increased 14-fold, within the first year after
discontinuing the lithium." There are increased cases of
goiter in 100 patients taking lithium that was related to dose
and duration. This was prevented by thyroxine.
Bipolar
Disord 1999 Sep;1(1):5-10
Perspectives on lithium treatment of bipolar disorder: action,
efficacy, effect on suicidal behavior.
Schou M.
The Psychiatric Hospital, Risskov, Denmark
In bipolar disorder the choice of prophylactic drug must
be based on a weighing of efficacy against tolerability, interactions,
ease of management, use during pregnancy and lactation, and expense.
Lithium should be the preferred prophylactic drug in patients
with typical bipolar disorder and in patients who are at high
risk of committing suicide, that is, patients with severe depressions
or depressions combined with persistent suicidal ideas or with
suicide attempts in the past.
Antidepressants
Mood
stabilizers taken with newer (second generation) antidepressants
induce mania less than older antidepressants - tricyclics and
MAOI.
Bupropion
(Wellbutrin), sertraline (Zoloft), and venlafaxine (Effexor) are
examined in consumers with the bipolar disorder who experience
"break through depression," even though medicated.
There
is a moderate antidepressant response in 33% and a 12% rate of
triggering mania in this study of 100 bipolars.
Buproprion
(Wellbutrin) vs. Desipramine (Norpramin) were studied. The rate
of cycling between mania and hypomania was significantly greater
in the Desipramine group (37%). Buproprion (13%,p<0.05).
Paxil
studied in a randomized, controlled six week trial. It was found
to be "equally effective for depression breaking through
ongoing mood stabilizer treatment as an addition of a second mood
stabilizer, typically valproate to lithium, or vice versa."
"...the
risk of depressive relapse for 27 bipolar patients after antidepressant
discontinuation was 67% versus 39% in the 18 patients who"
stayed on their antidepressants.
Mood
Stabilizers
The
treatment of combining one or more mood stabilizers with an antidepressant
to prevent manic episodes, needs to be explored further.
"...using
the newer antidepressants earlier to supplement mood stabilizers
should be considered."
New
medication and combining medications can produce remarkable improvement.
Lamotrigine
(Lamictal)
Lamotrigine
(Lamictal) has assisted many consumers whose illness has not responded
to other treatments. (Frye et al, 2000, J Clin Psychopharmacol,
in press; Calabrese et al., 1999, J Clin Psychiatry 60:
79-88).
Proceed
slowly with Lamictal to reduce risk of rash and other side effects.
Lamotrigine
(Lamictal) was superior to both gabapentin and placebo in a six-week
monotherapy trial for refractory patients.
437
outpatient study, double-blind, placebo-controlled; Lamotrigine
is equal to desipramine and superior to placebo in unipolar depression.
Gabapentin
(Neurontin)
Gabapentin
(Neurontin) is helpful for residual manic and depressive symptoms,
but not rapid cycling. Neurontin has better response with patients
who are associated with younger age, shorter duration of illness,
and lower initial body weight. Gabapentin failed to exceed placebo
in an outpatient study of acute mania.
Gabapentin
is not an effective medication for acute mania. Study: 10 wk.,
double-blind, placebo-controlled trial dosed between 900 and 3600
mg/day. Gabapentin was "not superior to the placebo for bipolar
I symptoms of hypomania, mania, or mixed states."
Gabapentin
has also been "effective in some anxiety disorders including
social phobia and is widely used for adjunctive treatment in pain
syndromes."
218
patient study of Gabapentin in the treatment of bipolar disorder
shows that if it is "combined with antidepressants, neuroleptics,
lithium, and other anticonvulsants, had a high rate of response
in combination (69%) and in monotherapy (42%)."
Bipolar
Disord 1999 Sep;1(1):61-5
Altshuler LL, Keck PE Jr, McElroy SL, Suppes T, Brown ES, Denicoff
K, Frye M, Gitlin M, Hwang S, Goodman R, Leverich G, Nolen W,
Kupka R, Post R.
UCLA Mood Disorders Research Program, UCLA Medical Plaza,
CA 90095-7057, USA
Gabapentin appears to have acute anti-manic and anti-depressant
properties as an adjunctive agent for refractory bipolar illness.
Prospective double-blind studies are needed to further delineate
its acute efficacy when used as monotherapy and its prophylactic
efficacy as monotherapy or in conjuction with other mood stabilizers.
Divalproex
(Depakote)
Divalproex
(Depakote) vs. Lithium were both equally effective in 43 patients.
The patients that did not respond to Lithium, responded to Depakote
and vice versa. "Depakote monotherapy was notably effective
in treating depressive symptoms."
Topiramate
(Topamax)
Topiramate
(Topamax) find a 56% much or very much improved response in "16
patients after 6 weeks, four of the 16 had unpleasant sense of
touch and two had word finding difficulties," in the treatment
of bipolar disorder. All patients lost weight at an average of
10 pounds.
"Dr.
R. McIntyre and colleagues at the Centre for Addiction and Mental
Health, Toronto, compared topiramate (50-300 mg/day) to bupropion
SR (Wellbutrin, 100-400 mg/day) for eight weeks as adjuncts to
mood stabilizers in 26 bipolar out patients with major depression.
Both bupropion SR and topiramate showed a significant reduction
in depressive symptoms and were not statistically different from
each other. No patients switched into a manic episode on either
treatment. These preliminary results suggest that topiramate may
have comparable antidepressant activity to bupropion SR, a remarkable
finding if replicated."
Mexiletine
(Mexitil)
Mexiletine
(Mexitil) has anticonvulsant, antiarrhythmic, and analgesic properties.
In a study of 13 treatment resistant bipolars at doses from 200
- 1200 mg/day had a full response in 45% of patients. Another
study: 8 out of 26 patients treated with Mexiletine had
a positive therapeutic effect.
ECT
(Electro Convulsive Therapy)
"...low
dose, right unilateral (one-sided) was ineffective in two different
studies of major depression (i.e., 23% improvement or 17% improvement
respectively). However, high dose right unilateral ECT was as
effective as bilateral (two-sided) ECT, and bilateral ECT clearly
produced more lasting amnesia and memory defects. (Sackeim et
al, 2000; Arch Gen Psychiatry 57: 425-434).
rTMS
and ECT are generally equally effective in "patients with
nondelusional major depression.
ECT
superior to patients with delusional depression than rTMS.
Bipolar
Brains
Study
of 10 bipolar brains during autopsy compared with "11 nonpsychiatric
control subjects.
Dr.
Rajkowska found decreased density of layer 3 in the dorsolateral
pre-frontal cortex (Brodman's area nine), comprised of a decrease
in the numbers of pyramidal cells but not other neuronal elements,
a decrease in glial cell density, and an increase in glial size."
"...bipolar
patients showed: 1) decreased dorsolateral prefrontal cortex NAA
bilaterally; 2) decreased prefrontal white matter NAA bilaterally;
and, 3) increased thalamic NAA bilaterally.
These
data thus supplement a growing amount of structural imaging data
suggesting alterations in size or chemistry of the prefrontal
cortex, amygdala, and hippocampus in bipolar patients compared
with controls."
Neuroleptics
Olanzapine
(Zyprexa)
Olanzapine
(Zyprexa) was statistically significantly superior to placebo
in the treatment of rapid cycling Bipolar I patients.
Bipolar
Disord 2000 Sep;2(3 Pt 1):196-9
Ghaemi SN, Cherry EL, Katzow JA, Goodwin FK.
Harvard Bipolar Research Program, Massachusetts General Hospital,
Consolidated Department of Psychiatry, Boston 02114, USA.
"Olanzapine appears to be moderately effective in open
add-on treatment in patients with mainly depressive symptoms.
Accumulating evidence suggests that olanzapine, and atypical antipsychotics
in general, possess mild to moderate adjunctive antidepressant
properties."
"Dr.
R. Baker and co-workers from Lilly Research Laboratories and Harvard
Medical School found that in two inpatient double-blind, randomized
trials investigating the efficacy of olanzapine for acute mania,
worsening of mania occurred more often on placebo than on olanzapine,
in contrast to previous reports in open trials that olanzapine
induced or exacerbated mania."
"Dr.
J. Frazier from Harvard Medical School and colleagues conducted
a study of olanzapine monotherapy (2.5-20 mg/day) in 23 juvenile
bipolar patients (ages 5-14) with mania or mixed symptoms. Sixty-one
percent of patients responded, and 22 (96%) of 23 completed the
study. Clinically significant increases in weight occurred in
some patients, however."
"Dr.
M. Tohen of Lilly Research Laboratories and Harvard Medical School,
along with colleagues from a variety of universities, performed
several studies with olanzapine. A three-week, double-blind study
of olanzapine (5-20 mg/day) versus valproate (500-2500 mg/day)
in hospitalized manic patients showed a statistically significant
greater improvement on olanzapine."
Cognitive
Therapy
6
month follow up showed fewer bipolar episodes, higher social functioning,
and better coping strategies "compared with the control group
that received treatment as usual. There was no evidence that the
improvement in the therapy group was due to more medications being
prescribed."
Being
able to identity early stages of relapse is very effective in
regards to the length of time the relapse lasts.
"To
date there are six controlled studies of CBT interventions with
children. All are school-based studies of children with self-reported
(but not with diagnosed) depression. Five of the six support the
efficacy of CBT in reducing depressive symptoms. There is considerable
variation in the nature of the CBT interventions.
"There
are nine controlled or comparative studies of CBT for adolescent
depression, seven of which found CBT efficacious at the end of
acute treatment. Most include adolescents with diagnosed depressive
disorders, and only one was conducted in a school setting.
"...there
is a question about whether CBT, medication, or combination treatment
is more efficacious with depressed teenagers or with certain subgroups
of these young people."
John F. Curry, Duke University Medical Center "Specific
Psychotherapies for Childhood and Adolescent Depression"
New
Research
17
to 24 year olds with bipolar spectrum disorders "reported
higher lifetime rates of anxiety, substance abuse, Attention Deficit-Hyperactivity
Disorder (ADHD), and eating disorders in bipolar than in unipolar
depressed participants. Women with bipolar disorder had higher
rates of anxiety (85% vs. 41%), ADHD (18% vs. 5%), and eating
disorders (15% vs. 0%) than men with bipolar disorder, but not
substance abuse disorders (41% vs. 32%)."
"A
recent National DMDA [Depressive and Manic-Depressive Association]
survey of people with bipolar disorder indicated that the average
length of time from onset of symptoms to correct diagnosis was
10 years."
Lydia Lewis, National DMDA "Unmet Needs in Diagnosis
and Treatment of Mood Disorder in Children and Adolescents"
"More
than 400 case reports and small trials have been reported on the
treatment of bipolar children and adolescents...Positive reports
have been published for lithium, divalproex, and carbamazepine;
however, many reports have been based on retrospective chart reviews
and small open-label studies...few placebo-controlled trials for
bipolar, manic or mixed, in children and adolescents have been
conducted."
Graham J. Emslie and Tarym L Mayes, University of Texas
Southwestern Medical Center "Mood Disorder in Children
and Adolescents: Psychopharmacological Treatment"
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The following is an excerpt of "A Five-Year Prospectus of the Stanley Foundation Bipolar Network (SFBN)"
at Stanley Foundation
Bipolar Network. You can get your own PDF copy there.
The last five years of research summarized:
...Treatment Findings:
8. An ongoing double-blind, randomized comparative trial of three of the newer
antidepressants (bupropion [Wellbutrin®], sertraline [Zoloft®], and venlafaxine
[Effexor®]) for bipolar depression (the largest comparative study to date) has
already indicated a good overall efficacy and a much lower than anticipated
switch rate into mania with the use of any of the three antidepressants when
they are added to an ongoing mood stabilizer for the treatment of breakthrough
depression.
9. The atypical antipsychotic olanzapine (Zyprexa®) was suggested to have utility in
the open add-on treatment of inadequately stabilized patients with bipolar
illness. These new data preceded and predicted its current status as an
FDA approved drug for the treatment of mania.
10. A number of the prominent antidepressant and potential mood-stabilizing
effects identified for the newly-approved anticonvulsant lamotrigine (Lamictal®)
have now been replicated in double-blind controlled clinical trials in the
literature and in the Stanley Foundation-supported clinical trials in the NIMH
Biological Psychiatry Branch.
11. A suggestive role for gabapentin (Neurontin®) as an adjunctive treatment, but
not in monotherapy, has been revealed.
12. Topiramate (Topamax®) appears to have useful adjunctive effects in patients with
unstable mood cycling, but does not appear to be a useful acute antidepressant.
Its prominent positive side-effects profile of inducing weight loss has now been
documented in a large cohort of affectively-ill patients similar to that first noted
in patients with seizure disorders.
13. An apparent lack of efficacy of the new anticonvulsant tiagabine (Gabitril®) and
the potential for serious side effects, such as the occurrence of seizures in
patients without a prior history of seizure disorder, has been rapidly elucidated.
14. Placebo-controlled trials of the potential antidepressant, antimanic, and moodstabilizing
effects of the specific omega-3 fatty acid EPA (eicosapentaenoic acid)
are in progress with more than 50 patients randomized.
15. Protocols for a new series of clinical trials with novel agents are in place and are
being reviewed by local IRBs.
16. The ongoing study and treatment of this large and well-characterized cohort of
patients makes recruitment for clinical trials much more efficient and rapid than
could be accomplished by usual cumbersome single-study recruitment
techniques in the field. In fact, the Network strategy for following a large cohort
of patients in continuous follow-up has been adopted by two large NIMH funded
programs in unipolar depression (STAR*D) and in bipolar illness (the STEPBP
program).
17. Based on the computerized longitudinal database we are evaluating optimal
medication combination treatments based on long-term treatment outcome..."
Demographic and clinical characteristics of individuals in a bipolar disorder case registry.
Kupfer DJ, Frank E, Grochocinski VJ, Cluss PA, Houck PR, Stapf DA.
Department of Psychiatry, University of Pittsburgh School of Medicine, Western Psychiatric Institute and Clinic, PA 15213, USA. kupferdj@msx.upmc.edu
BACKGROUND: The goal of this analysis was to characterize a cohort of 3000 persons who self-identified as having bipolar disorder by demographic, clinical, and treatment characteristics and to document the burden that this disorder imposed on their lives. METHOD: The Stanley Center Bipolar Disorder Registry used a variety of recruitment methods to reach people with bipolar disorder. The cohort included those currently in treatment and those active in support groups. Registrants completed an interviewer-administered questionnaire to obtain information on demographic characteristics, clinical history, and treatment history. RESULTS: The median age of the 2839 patients who were analyzed was 40.1 years, 64.5% were women, and over 90% were white. The median age at onset was 17.5 years, and the mean was 19.8 years. Despite the fact that over 60% completed at least some college and 30% completed college, 64% were currently unemployed. The patients' family histories point to a high prevalence of mental disorder in the families, especially mood disorders. Patients were concurrently taking multiple medications, and more than one third were taking at least 3 types of psychotropic medications. This pattern of pharmacotherapy was consistent with participants' overall mood ratings, which demonstrated how unusual it was for them to be symptom-free over a 6-month period. CONCLUSION: Our present findings point to the chronicity and severity of bipolar disorder as experienced in the community. We still need to develop better interventions, ensure access to care consistent with current consensus guidelines, and initiate care as early as possible in the course of the condition.
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The above information is used only for educational
purposes and not for profit.
"(The
BNN is published four times a year by an international group of
investigators working with patients with bipolar disorder to better
understand the long-term course and treatment of the illness.
The goal of the Network is to help develop new and more effective
treatments for bipolar disorder. http://www.bipolarnetwork.org,
email: info@bipolarnetwork.org)"
Last Updated: 10/09/06