Expert: Ivan Goldberg, M.D. - 9/17/2006

Question
Hi!  My wife has bipolar and severe Irritible Bowel Syndrome (a stress-related problem of the colon being over or under active, with pain/nausea).  Her GI Dr. thought that the extended bout (76 days) of her IBS is totally due to her depression that occurred about the same time as the beginning of this extremely long bout.  She is on GI meds, as well as Paxil 40mg and Klonopin 3mg/day.  The psychiatrist also put her back on Seroquel.  1. Does Seroquel also treat depression (I thought it was for mania) or whatever this may be? 2. How long does it take for the Seroquel to kick back in after resuming it?  Thanks!  Ken (another allexpert-astronomy).

Answer
Hi, Ken . . .

Seroquel is useful as a treatment of both the manic and depressive phases of bipolar disorder. it often takes up to a month for it to kick in, and a final dose between 300 and 600 mg a day.

Here are a few abstracts on the topic:

1: Can J Psychiatry. 2006 Jul;51(8):523-30.

Add-on quetiapine for bipolar depression: a 12-month open-label trial.

Milev R, Abraham G, Zaheer J.

Department of Psychiatry, Queen's University, Kingston, Ontario.
milevr@pccchealth.org

OBJECTIVES: Bipolar disorder (BD) is a disabling and often chronic condition.
Patients with BD suffer from depression at least one-third of the time, but they
do not always respond well to conventional mood stabilizers. Attempts to treat
them with antidepressants can provoke a switch to mania or increased cycling.
Our open-label trial aimed to assess the long-term response of patients with
bipolar depression to the addition of quetiapine to their usual treatment. Our
study also sought to assess the safety and tolerability of quetiapine in
patients with BD. METHOD: To meet inclusion criteria for the study, patients had
a DSM-IV diagnosis of type I or II BD, were aged 18 years and older, currently
suffered from depression with a score of > 18 on the Hamilton Depression Rating
Scale (HDRS), and had no change in antidepressant use for at least 3 weeks prior
to the study. We added quetiapine to patients' medication and attempted to
increase the dosage to at least 400 mg daily. Outcome was measured at baseline
and once monthly for 12 months on the HDRS, the Young Mania Rating Scale, the
Clinical Global Impression Scale (CGI), and the Abnormal Involuntary Movement
Scale. RESULTS: There were 19 patients enrolled in the study (6 men and 13
women), 2 of whom dropped out because they could not tolerate the drug.
Seventeen completed at least 2 assessments, and 7 patients completed the full
12-month trial. Data for the 17 patients (that is, last observation carried
forward) at 12 months shows HDRS scores reduced from 27.2 to 12.1 and CGI scores
reduced from 4.7 to 2.6. CONCLUSIONS: Quetiapine seems to be helpful to and
relatively well tolerated by patients with bipolar depression when it is added
to their usual treatment. There is, however, a need for controlled trials.



2: J Clin Psychiatry. 2005 Nov;66(11):1376-85.

Typical and atypical antipsychotics in bipolar depression.

Gao K, Gajwani P, Elhaj O, Calabrese JR.


Mood Disorders Program, Department of Psychiatry, University Hospitals of
Cleveland, Case Western Reserve University School of Medicine, 11400 Euclid
Avenue, Cleveland, OH 44106, USA. keming.gao@uhhs.com

BACKGROUND: Symptomatic bipolar patients experience more depressive than manic
symptoms, but fewer studies have been designed for bipolar depression than for
bipolar mania. Since the antipsychotic agents have been shown to diminish
depressive symptoms during the treatment of mania, atypical agents are now being
studied for use in bipolar depression. DATA SOURCES: English-language articles
published from 1980 through July 2004 and cited in MEDLINE were searched using
the keywords antipsychotics, typical antipsychotics, atypical antipsychotics,
bipolar depression, bipolar disorder, manic-depressive illness, placebo, and
clinical trial. The generic and brand names of individual antipsychotics were
also entered as keywords. Peer-reviewed abstracts of placebo-controlled studies
assessing acute or long-term efficacy in bipolar depression presented at major
scientific meetings were also reviewed. STUDY SELECTION: Use of a depression
rating scale was required for inclusion of studies of the atypical antipsychotic
agents in our analysis. DATA SYNTHESIS: Twenty-one randomized trials and 13
nonrandomized prospective trials were identified. In the only 2 acute,
double-blind, placebo-controlled studies of antipsychotics in bipolar
depression, the effect size of olanzapine was small (0.32) compared with the
effect sizes of quetiapine (0.91-1.09, depending on dose). The effect size in
acute mania of olanzapine at week 4 and quetiapine at week 3 was 0.50 and 0.39,
respectively. Both olanzapine and quetiapine have been shown to be superior to
placebo in the acute treatment of bipolar I depression. In addition, olanzapine
has been shown to be more effective than placebo in delaying relapse into
bipolar depression. With the exception of a 6-month perphenazine study, there
are no other randomized studies of typical antipsychotics that support the
conclusion that this class of medication worsens bipolar depression. CONCLUSION:
Emerging data suggest that the atypical antipsychotic agents have a role in the
acute and long-term treatment of bipolar depression. No convincing data support
the impression that the typical antipsychotic agents worsen bipolar depression.



3: Bipolar Disord. 2005;7 Suppl 5:13-23.

Newer treatment studies for bipolar depression.

Gao K, Calabrese JR.

NIMH Bipolar Research Center, Mood Disorders Program, University Hospitals of
Cleveland/Case Western Reserve University School of Medicine, Cleveland, OH,
USA. keming.gao@uhhs.com

OBJECTIVE: Depressive symptoms of bipolar disorder have more negative impact on
a patient's life than manic symptoms. This review focused on the emerging
efficacy data for treatments in bipolar depression. METHODS: English-language
literature cited in Medline was searched with terms bipolar depression, clinical
trial, and trial. Randomized, placebo-controlled trials of newer studies with
older agents and all studies with newer or novel agents were prioritized.
Open-label studies of novel agents presented at major scientific meetings were
also included. RESULTS: Olanzapine, olanzapine-fluoxetine combination (OFC), and
quetiapine were superior to placebo in the acute treatment of bipolar
depression. Lamotrigine only significantly reduced core symptoms of depression
compared with placebo. Pramipexole, a dopamine D2/D3 receptor agonist and
omega-3 fatty acids, a polyunsaturated fatty acid, augmentation to mood
stabilizer (MS) had superiority to placebo in reducing depressive symptoms.
Topiramate augmentation of an MS was equally as effective as Bupropion-SR.
Patients treated with an MS responded well to the addition of agomelatine, a
melatonin receptor agonist with 5-HT2C antagonist properties. However, inositol
and repetitive transcranial magnetic stimulation did not separate from placebo.
Lamotrigine and olanzapine, and to a lesser extent, divalproex, are superior to
placebo in preventing depressive relapses. All agents were relatively well
tolerated. CONCLUSIONS: Olanzapine, OFC, and quetiapine are effective in the
acute treatment of bipolar depression. Compared with lithium and divalproex,
lamotrigine is more effective in preventing bipolar depression. Larger
controlled studies of the other agents in the acute and maintenance treatment of
bipolar depression are warranted.



4: Am J Psychiatry. 2005 Jul;162(7):1351-60.

A randomized, double-blind, placebo-controlled trial of quetiapine in the
treatment of bipolar I or II depression.

Calabrese JR, Keck PE Jr, Macfadden W, Minkwitz M, Ketter TA, Weisler RH, Cutler
AJ, McCoy R, Wilson E, Mullen J.

University Hospitals of Cleveland and Case University School of Medicine, 11400
Euclid Ave., Suite 200, Cleveland, OH 44106, USA. joseph.calabrese@uhhs.com

OBJECTIVE: There is a major unmet need for effective options in the treatment of
bipolar depression. METHOD: Five hundred forty-two outpatients with bipolar I
(N=360) or II (N=182) disorder experiencing a major depressive episode (DSM-IV)
were randomly assigned to 8 weeks of quetiapine (600 or 300 mg/day) or placebo.
The primary efficacy measure was mean change from baseline to week 8 in the
Montgomery-Asberg Depression Rating Scale total score. Additional efficacy
assessments included the Hamilton Depression Rating Scale, Clinical Global
Impression of severity and improvement, Hamilton Anxiety Rating Scale,
Pittsburgh Sleep Quality Index, and Quality of Life Enjoyment and Satisfaction
Questionnaire. RESULTS: Quetiapine at either dose demonstrated statistically
significant improvement in Montgomery-Asberg Depression Rating Scale total
scores compared with placebo from week 1 onward. The proportions of patients
meeting response criteria (> or =50% Montgomery-Asberg Depression Rating Scale
score improvement) at the final assessment in the groups taking 600 and 300
mg/day of quetiapine were 58.2% and 57.6%, respectively, versus 36.1% for
placebo. The proportions of patients meeting remission criteria
(Montgomery-Asberg Depression Rating Scale < or =12) were 52.9% in the groups
taking 600 and 300 mg/day of quetiapine versus 28.4% for placebo. Quetiapine at
600 and 300 mg/day significantly improved 9 of 10 and 8 of 10 Montgomery-Asberg
Depression Rating Scale items, respectively, compared to placebo, including the
core symptoms of depression. Treatment-emergent mania rates were low and similar
for the quetiapine and placebo groups (3.2% and 3.9%, respectively).
CONCLUSIONS: Quetiapine monotherapy is efficacious and well tolerated for the
treatment of bipolar depression.

Best regards . . .

Ivan
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