Anyone reading this blog more than a few times would know that I’m no fan of the STAR*D sequential antidepressant study [a thirty-five million dollar misunderstanding…]. And besides the objections to the study itself and the fact that the authors have never published the results of the primary outcome variable [HAM-D], I object to the flooding of the literature with well over 100 other articles by a coven of authors that feel like resume fillers rather than scientific contributions. So when I saw yet another STAR*D offering in the June American Journal of Psychiatry, I approached it with a skeptical eye. It was a study about the children of depressed mothers and how these kids responded to their mother’s response to antidepressants in the year following their mother’s treatment [Children of depressed mothers 1 year after remission of maternal depression: findings from the STAR*D-Child study.][not online in the full text version]. I wouldn’t for a minute want to argue against the fact that children of depressed mothers would be a lot better off if their mothers got better, but there was something about the paper that bothered me. Rush et. all have always insisted that depressed people should be treated vigorously "to remission." It frankly bothers me that they talk is as if the antidepressants are specifically treating the disease "depression." To me that specificity is unproven, and I don’t think there’s clinical justification to call MDD a disease. I’ve been suspicious that the injunction was more part of their pharma-driven campaign to use more antidepressants than based on some clinical observation.
But something else bothered me. The study looked familiar – like something I’d already read. Indeed, I had run across the same study, or something very close when I was reviewing STAR*D earlier this year. It was from 2008 and is available in full text online [Children of Depressed Mothers 1 Year After the Initiation of Maternal Treatment: Findings From the STAR*D-Child Study.]. And when I found that study, it referred me to an even earlier paper in the JAMA [Remissions in maternal depression and child psychopathology: a STAR*D-child report.], also online full text. As it turns out, all three articles are about the exact same cohort of patients and a confidence in those medications that seems inflated.
I’ve put the abstracts below for perusal [these patients were actually treated between 2001 and 2004]:
Remissions in maternal depression and child psychopathology: a STAR*D-child report.
by Weissman MM, Pilowsky DJ, Wickramaratne PJ, Talati A, Wisniewski SR, Fava M, Hughes CW, Garber J, Malloy E, King CA, Cerda G, Sood AB, Alpert JE, Trivedi MH, Rush AJ; STAR*D-Child Team.
JAMA. 2006 22;295(12):1389-98.
CONTEXT: Children of depressed parents have high rates of anxiety, disruptive, and depressive disorders that begin early, often continue into adulthood, and are impairing.OBJECTIVE: To determine whether effective treatment with medication of women with major depression is associated with reduction of symptoms and diagnoses in their children.DESIGN: Assessments of children whose depressed mothers were being treated with medication as part of the multicenter Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial conducted (between December 16, 2001 and April 24, 2004) in broadly representative primary and psychiatric outpatient practices. Children were assessed by a team of evaluators not involved in maternal treatment and unaware of maternal outcomes. Study is ongoing with cases followed at 3-month intervals.SETTING AND PATIENTS: One hundred fifty-one mother-child pairs in 8 primary care and 11 psychiatric outpatient clinics across 7 regional centers in the United States. Children were aged 7 to 17 years.MAIN OUTCOME MEASURES: Child diagnoses based on the Kiddie Schedule for Affective Disorders and Schizophrenia; child symptoms based on the Child Behavior Checklist; child functioning based on the Child Global Assessment Scale in mothers whose depression with treatment remitted with a score of 7 or lower or whose depression did not remit with a score higher than 7 on the Hamilton Rating Scale for Depression.RESULTS: Remission of maternal depression after 3 months of medication treatment was significantly associated with reductions in the children’s diagnoses and symptoms. There was an overall 11% decrease in rates of diagnoses in children of mothers whose depression remitted compared with an approximate 8% increase in rates of diagnoses in children of mothers whose depression did not. This rate difference remained statistically significant after controlling for the child’s age and sex, and possible confounding factors (P = .01). Of the children with a diagnosis at baseline, remission was reported in 33% of those whose mothers’ depression remitted compared with only a 12% remission rate among children of mothers whose depression did not remit. All children of mothers whose depression remitted after treatment and who themselves had no baseline diagnosis for depression remained free of psychiatric diagnoses at 3 months, whereas 17% of the children whose mothers remained depressed acquired a diagnosis. Findings were similar using child symptoms as an outcome. Greater level of maternal response was associated with fewer current diagnoses and symptoms in the children, and a maternal response of at least 50% was required to detect an improvement in the child.CONCLUSIONS: Remission of maternal depression has a positive effect on both mothers and their children, whereas mothers who remain depressed may increase the rates of their children’s disorders. These findings support the importance of vigorous treatment for depressed mothers in primary care or psychiatric clinics and suggest the utility of evaluating the children, especially children whose mothers continue to be depressed.
Children of depressed mothers 1 year after the initiation of maternal treatment: findings from the STAR*D-Child Study
by Pilowsky DJ, Wickramaratne P, Talati A, Tang M, Hughes CW, Garber J, Malloy E, King C, Cerda G, Sood AB, Alpert JE, Trivedi MH, Fava M, Rush AJ, Wisniewski S, and Weissman MM.
American Journal of Psychiatry. 2008 165[9]:1136-47.
OBJECTIVE: Maternal depression is a consistent and well-replicated risk factor for child psychopathology. The authors examined the changes in psychiatric symptoms and global functioning in children of depressed women 1 year following the initiation of treatment for maternal major depressive disorder.METHOD: Participants were 1) 151 women with maternal major depression who were enrolled in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study and 2) their eligible offspring who, along with the mother, participated in the child STAR*D (STAR*D-Child) study (mother-child pairs: N=151). The STAR*D study was a multisite study designed to determine the comparative effectiveness and acceptability of various treatment options for adult outpatients with nonpsychotic major depressive disorder. The STAR*D-Child study examined children of depressed women at baseline and involved periodic follow-ups for 1 year after the initiation of treatment for maternal major depressive disorder to ascertain the following data: 1) whether changes in children’s psychiatric symptoms were associated with changes in the severity of maternal depression and 2) whether outcomes differed among the offspring of women who did and did not remit (mother-child pairs with follow-up data: N=123). Children’s psychiatric symptoms in the STAR*D-Child study were assessed using the Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version (K-SADS-PL), and maternal depression severity in the STAR*D study was assessed by an independent clinician, using the 17-item Hamilton Depression Rating Scale (HAM-D).RESULTS: During the year following the initiation of treatment, maternal depression severity and children’s psychiatric symptoms continued to decrease over time. Decreases in the number of children’s psychiatric symptoms were significantly associated with decreases in maternal depression severity. When children’s outcomes were examined separately, a statistically significant decrease in symptoms was evident in the offspring of women who remitted early (i.e., within the first 3 months after the initiation of treatment for maternal depression) or late (i.e., over the 1-year follow-up interval) but not in the offspring of nonremitting women.CONCLUSIONS: Continued efforts to treat maternal depression until remission is achieved are associated with decreased psychiatric symptoms and improved functioning in the offspring.
Children of depressed mothers 1 year after remission of maternal depression: findings from the STAR*D-Child study.
by Wickramaratne P, Gameroff MJ, Pilowsky DJ, Hughes CW, Garber J, Malloy E, King C, Cerda G, Sood AB, Alpert JE, Trivedi MH, Fava M, Rush AJ, Wisniewski S, and Weissman MM.
American Journal of Psychiatry. 2011 168[6]:593-602.
OBJECTIVE: Maternal major depressive disorder is an established risk factor for child psychopathology. The authors previously reported that 1 year after initiation of treatment for maternal depression, children of mothers whose depression remitted had significantly improved functioning and psychiatric symptoms. This study extends these findings by examining changes in psychiatric symptoms, behavioral problems, and functioning among children of depressed mothers during the first year after the mothers’ remission from depression.METHOD: Children were assessed at baseline and at 3-month intervals with the Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version, the Child Behavior Checklist, and the Children’s Global Assessment Scale for 1 year after their mothers’ remission or for 2 years if the mothers did not remit. The authors compared children of early remitters (0-3 months; N=36), late remitters (3-12 months; N=28), and nonremitters (N=16).RESULTS: During the postremission year, children of early-remitting mothers showed significant improvement on all outcomes. Externalizing behavioral problems decreased in children of early- and late-remitting mothers but increased in children of nonremitting mothers. Psychiatric symptoms decreased significantly only in children of mothers who remitted, and functioning improved only in children of early-remitting mothers.CONCLUSIONS: Remission of mothers’ depression, regardless of its timing, appears to be related to decreases in problem behaviors and symptoms in their children over the year after remission. The favorable effect of mothers’ remission on children’s functioning was observed only in children of early-remitting mothers.
The 2006 report compared the children’s symptoms at three months of maternal treatment between the mothers who remitted [HAM-D < 7] and those who didn’t. The second report [2008] made the same comparison at 1 year from the mother’s entering the study. And this recent report compared the children’s score after 1 year from the time the mother’s depression remitted or the mother’s symptom continued for 1 year without remission. Here are the respective conclusions [and mine]:
• 2006: Remission of maternal depression has a positive effect on both mothers and their children, whereas mothers who remain depressed may increase the rates of their children’s disorders. These findings support the importance of vigorous treatment for depressed mothers in primary care or psychiatric clinics and suggest the utility of evaluating the children, especially children whose mothers continue to be depressed.
The 2006 report appears to me to be a conclusion in search of a study. All of the mothers in this group were being "vigorously" treated. They reported that the children of the mothers who did not remit had more psychiatric symptoms. I don’t get their conclusion. To me the study points to the limitations of the effectiveness of the current antidepressants, and suggest that those limits are felt by the depressed mother’s kids.
• 2008: Continued efforts to treat maternal depression until remission is achieved are associated with decreased psychiatric symptoms and improved functioning in the offspring.
Again they report that the kids of mother’s who remitted did better. But in STAR*D, all of these mothers had "continued efforts to treat maternal depression." The actual conclusion would be something like, "If the mother responds to the continued efforts to treat her depression, the kids do better." Nothing more than that is justified from the study. STAR*D did not have a group [untreated or placebo] for comparison to justify their conclusion.
• 2011: Remission of mothers’ depression, regardless of its timing, appears to be related to decreases in problem behaviors and symptoms in their children over the year after remission. The favorable effect of mothers’ remission on children’s functioning was observed only in children of early-remitting mothers.
2011 is a different time. By now, people are beginning to question a lot of the drug research and its accuracy. This 2011 article only concludes the more obvious – that mothers who recover quickly have less observed symptoms in their children. So maybe the recent push for more rational evaluation of the results of these endless drug trials is working. Or is it? In the next post, I propose that we take a look at this most recent study and see if the results justify even these modulated conclusions. Again, I won’t argue against the idea that helping depressed mothers helps kids. But I will question that these studies nail that point, or that they say anything that supports the call for "vigorous drug treatment." My real focus is not the conclusions themselves, it’s on what I consider to be the flawed nature of the STAR*D data and its analysis.
It has always bothered me the way they run clinical “trials” in this country. Its all about the patent and the profit, not the patient. Not only do they rarely run their drug up against an “active placebo” and/or an existing drug during efficacy tests, they cherry pick the participants for best results. Then they go and do everything they can to market the new junk, AKA hide the good old stuff, and pass out brownie points to doctors. That, in turn, passes on much higher costs to patients. I own a PDR. I know there are MANY drugs that are much safer and/or cheaper and more effective than the seemingly ~100 that ever make it to pharmacy shelves. Today I had to go to 2 different pharmacies to fill 2 different prescriptions. That’s a BAD sign and we pay more for Rx drugs than any other country on earth (dozens, sometimes hundreds of TIMES more)!
Seems you have a glitch… I left a comment but the link to this page is telling me “no comments”. I donno
Thanks Mickey for posting this. It is hard to stay on top of the ongoing publication of STAR*D articles that have nothing to do with its original purpose.
The opening paragraph of STAR*D’s Research Protocol states in capital letters that it was to be a COMPARATIVE EFFECTIVENESS study of different treatment options for people with major depression. As such, the STAR*D researchers collected 11 pre-specified research outcome measures that were blindly-administered at entry into, and exit from, each treatment step, and every three months during the 12 months of follow-up care. These measures included the assessment of depressive symptoms, level of functioning, patient satisfaction, quality of life, side-effect burden, healthcare utilization and cost of care, health status, work productivity, and personal income.
The STAR*D Research Protocol included a detailed statistical analytic plan for using these measures to compare the cost-effectiveness of the various antidepressant treatments including their impact on overall healthcare utilization and cost-of-care. While many of us would argue that STAR*D’s research design was profoundly biased by not having a placebo-control condition in any of its multiple comparisons (among other flaws), the study at least had the benefit of collecting a wide range of blindly-administered measures to use in comparing outcomes from various antidepressant and cognitive therapy treatments.
However, despite having published 100+ articles, the researchers have still not reported any of the outcomes for these 11 pre-specified measures other than the Hamilton remission rates in the initial steps 1-4 articles. Instead, the STAR*D ‘researchers’ have mainly used the clinic-administered QIDS-SR as their outcome measure without disclosing to readers the fact that the Research Protocol explicitly excluded it from such use since it was non-blinded and one of the clinical management tools that was used to guide care.
To my knowledge, the STAR*D ‘researchers’ have never provided an explanation for why they have not reported the COMPARATIVE EFFECTIVENESS outcomes using the 11 pre-specified measures. Instead, all we get are resume building articles such as these that have nothing to do with why STAR*D received 35-million-dollars in taxpayer funding.