• Pregnant women with depression are at significantly greater risk of
preterm delivery than those without depression, a prospective, naturalistic,
cohort study shows.
Researchers at the Kaiser Foundation Research Institute analyzed data on
791 women who were interviewed for depressive symptoms at the early stage of
their pregnancy (about 10 weeks) and gave a live birth later within the Kaiser
Permenante medical program in the San Francisco area. Those who met the
criteria of significant depressive symptoms, determined by a score of 16 or
higher on the Center for Epidemiological Studies Depression Scale (CESD), had
nearly twice the risk (hazard ratio 1.9) of preterm delivery compared with
women with a CESD score below 16, after adjusting for other confounding
factors such as maternal age, education, a history of miscarriage or other
complications, and smoking. The effect increased with more severe depression
as women with a CESD score of 22 or above had a hazard ratio of 2.2, while
those with CESD score of 16 to 21 had a hazard ratio of 1.6. The author stated
that only 1.5 percent of the study cohort was prescribed any antidepressants
during the study period, and excluding these patients did not change the
conclusion. Therefore, the increased rate of preterm delivery was likely
related to the depression rather than medication use. The study was supported
in part by funds from the California Public Health Foundation.
Li D et al. Presence of Depressive Symptoms During Early Pregnancy
and the Risk of Preterm Delivery: A Prospective Cohort Study.Hum
Reprod.Published online October 23, 2008.
• Stroke survivors who develop depression are more likely to carry
certain genetic variations in the serotonin transporter gene (SERT), a study
has found. Specific polymorphisms in the serotonin-transporter-linked
polymorphic region (5-HTTLPR) and the STin2 variable number tandem repeats
(VNTR) in the intron 2 region were both significantly associated with the
likelihood of poststroke depression. The study authors compared 75 survivors
of ischemic strokes who had a score of 11 or greater on the 30-item Geriatric
Depression Scale (GDS) and a control cohort of 75 stroke survivors with a
score of less than 11. All study participants were recruited from a larger
study on the treatment of poststroke depression.
The s/s genotype in 5-HTTLPR and the 9/12 and 12/12 genotypes in STin2 VNTR
were associated with three to four times the likelihood of having poststroke
depression. The authors noted that carrying the s allele in 5-HTTLPR has been
associated with depression moderated by life stress, suicidal behavior,
bipolar disorder, and below-average response to antidepressant medications.
Carrying the risk alleles in STin2 VNTR has been linked to schizophrenia,
bipolar disorder, and depression.
The study was funded by the National Institute of Nursing Research,
National Institutes of Health, and the Veterans Affairs Puget Sound Health
Care System in Washington State.
Kohen R et al. Association of Serotonin Transporter Gene
Polymorphism With Poststroke Depression.Arch Gen Psychiatry.2008; 65(11):1296-1302.
• A new study links depression, but not antidepressant use, to
increased mortality in heart failure patients. The authors recruited patients
who were admitted to the cardiology service at Duke University Medical Center
for heart failure and followed them annually for vital status, depression, and
antidepressant treatment. Between March 1997 and June 2003, 1,006 patients
were enrolled in the study, including 30 percent with depression, defined as
having a Beck Depression Index (BDI) score of 10 or higher. Sixteen percent of
all patients were taking antidepressants. Within a mean follow-up length of
972 days, 429 (42.7 percent) patients died. The mortality rates were 53.3
percent in patients with depression and 38.1 percent in patients without
The association between the antidepressant use and increased mortality
disappeared after the authors controlled for depression and other confounding
factors. Depression itself was a significant risk factor for higher mortality,
with a hazard ratio of 1.33. The study was funded by the Duke Clinical
Research Institute and a grant from the National Institute of Mental
O'Connor CM et al. Antidepressant Use, Depression, and Survival in
Patients with Heart Failure.Arch Intern Med.2008;
• Iron deficiency during a woman's pregnancy has been linked to
increased risk of schizophrenia or related mental disorders in the offspring
in a recent epidemiological study. The authors matched 6,872 people with
available medical records between 1981 and 1997 and their mothers' hemoglobin
levels during pregnancy between 1959 and 1966. The mother-offspring cohorts
were derived from large population studies with data from the Kaiser
Permanente medical care plan in Alameda County, Calif.
People born to mothers with a low hemoglobin level (10.0 g/dL or less)
during pregnancy had a significantly higher rate of having a diagnosis of
schizophrenia spectrum disorders (SSDs, including schizophrenia,
schizoaffective disorder, delusional disorder, psychotic disorder not
otherwise specified, and schizotypal personality disorder) compared with those
born to mothers with a normal hemoglobin level (12.0 g/dL or above) with a
risk ratio of 3.73. Specifically, low maternal hemoglobin level in the second
and third trimesters was associated with significantly higher risk of SSDs in
offspring. The authors suggested that the lack of iron may directly or
indirectly affect the normal development of the brain through a number of
The study was funded by grants from the National Institute of Mental
Health, Frontier Fund of Columbia University, and Eunice Kennedy Shriver
Institute of Child Health and Human Development.
Insel BJ et al. Maternal Iron Deficiency and the Risk of
Schizophrenia in Offspring.Arch Gen Psychiatry.2008;
• Flunarizine, a calcium channel blocker used to treat migraine,
vertigo, and other indications, may also be an effective anti-psychotic to
treat schizophrenia, a randomized, controlled, double-blind study by a group
of Brazilian researchers has found. Seventy schizophrenia patients with stable
disease were randomized to receive either flunarizine (n=34) or haloperidol
(n=36) for 12 weeks; 25 and 27 patients, respectively, completed the entire 12
weeks. The mean total score on the Positive and Negative Syndrome Scale
(PANSS) was reduced by 21 percent from baseline in the flunarizine group and
by 19 percent in the haloperidol group; both were a statistically significant
improvement. The differences in PANSS total score, subscale scores, and the
Clinical Global Impression-Improvement scores were not statistically
significant between the two groups. The haloperidol group had significantly
higher treatment-related akathisia and weight gain, but the groups did not
differ significantly in extrapyramidal symptoms and prolactin levels.
Past research has shown that flunarizine is a dopamine D2
receptor antagonist with moderate affinity with no significant 5-HT receptor
blockade. It is not available in the United States but is sold in other
countries. The study was funded by the Stanley Medical Research Institute.
Bisol LW. Is Flunarizine a Long-Acting Oral Atypical Antipsychotic?
A Randomized Clinical Trial Versus Haloperidol for the Treatment of
Schizophrenia.J Clin Psychiatry. 2008; 69(10):
• A randomized, double-blind, head-to-head comparative trial of
olanzapine versus divalproex has shown no significant difference between the
two drugs in efficacy for the acute treatment of mild to moderate mania.
Bipolar patients in acute manic or mixed episodes with a Young Mania Rating
Scale (YMRS) total score of 20 to 30 (mild to moderate in severity) were
randomly assigned to three treatment groups: olanzapine (n=215), divalproex
(n=201), or placebo (n=105). After three weeks of treatment, the reduction in
YMRS total score from baseline was significantly different between the
olanzapine and placebo groups, but was not significantly different in the
olanzapine-versus-divalproex and divalproex-versus-placebo comparisons.
At the end of week 3, patients in the olanzapine and divalproex groups
continued with the same treatment for another nine weeks. At the end of week
12, the YMRS score reduction was significantly greater in olanzapine-treated
patients than divalproex-treated patients. The placebo group was switched to
olanzapine at the end of week 3, but they were not included in the 12-week
Patients in the olanzapine group had significantly larger increases in
weight and glucose, cholesterol, triglyceride, uric acid, and prolactin levels
than those in the divalproex group. Patients in the divalproex group had
significantly greater decreases in leukocytes and platelets than those in the
The study was funded by Eli Lilly and Co. and conducted in several
countries between October 2004 and December 2006.
Tohen M et al. Olanzapine Versus Divalproex Versus Placebo in the
Treatment of Mild to Moderate Mania: A Randomized, 12-Week, Double-Blind
Study.J Clin Psychiatry.Published online October 7,