Barry Duncan, Psy.D. barrylduncan@comcast.net Marcia Barbacki mbarbacki@att.net

www.heartandsoulofchange.com

The Use and Abuse of

Psychiatric Drugs

in Pregnancy

Women During Child Bearing

Years

Women During Child Bearing

YearsMDD affects b/w 7%

& 13%, peak age 25-44

BD affects b/w 4% & 6%, with onset in the teens to early 20s.

Schizophrenia affects about 1% during the early childbearing years.

MDD affects b/w 7% & 13%, peak age 25-44

BD affects b/w 4% & 6%, with onset in the teens to early 20s.

Schizophrenia affects about 1% during the early childbearing years.

Between 14% and 23% of pregnant women experience depressive symptoms, and approximately 13% of women in 2003 took an antidepressant at some time during pregnancy.

Between 14% and 23% of pregnant women experience depressive symptoms, and approximately 13% of women in 2003 took an antidepressant at some time during pregnancy.

Prevalence of SSRIsUsed During Pregnancy in the

US

Prevalence of SSRIsUsed During Pregnancy in the

US

13% in the US5% in CanadaIncreases in

Finland, Denmark, Israel, Germany, and Italy

Global increase of psych meds: 274%

13% in the US5% in CanadaIncreases in

Finland, Denmark, Israel, Germany, and Italy

Global increase of psych meds: 274%

Global Prevalence of SSRIsUsed During Pregnancy

Global Prevalence of SSRIsUsed During Pregnancy

What Is the Evidence Regarding Efficacy and

Safety?

What Is the Evidence Regarding Efficacy and

Safety?No RCTs w/pregnant

women, so all use is off-label

Have to rely on RCTs about meds in general pop. & on studies of the incidence of birth defects to address:

No RCTs w/pregnant women, so all use is off-label

Have to rely on RCTs about meds in general pop. & on studies of the incidence of birth defects to address:

Are Increasing Rates Justified by a Risk Benefit Analysis?

Are Increasing Rates Justified by a Risk Benefit Analysis?

More importantly, what should you, as physicians and health care professionals, know to conduct an informed discussion about treatments for emotional and behavioral problems during pregnancy?

More importantly, what should you, as physicians and health care professionals, know to conduct an informed discussion about treatments for emotional and behavioral problems during pregnancy?

Marcia Angell: “It is simply no longer possible to believe much of the clinical research that is published, or to rely on the judgment of trusted physicians or authoritative medical guidelines. I take no pleasure in this conclusion, which I reached slowly & reluctantly over my two decades as an editor of NEJM.”

Marcia Angell: “It is simply no longer possible to believe much of the clinical research that is published, or to rely on the judgment of trusted physicians or authoritative medical guidelines. I take no pleasure in this conclusion, which I reached slowly & reluctantly over my two decades as an editor of NEJM.”

Justified by the Clinical Trial Evidence?Hard to Get an Accurate Picture

Extends to Internet, print, & broadcast media, direct-to consumer-advertising, “grassroots” consumer-advocacy, prof. guilds, medical schools, docs, & research—even the FDA. So, press reports, web pages, & even academic literature can be unreliable.

Extends to Internet, print, & broadcast media, direct-to consumer-advertising, “grassroots” consumer-advocacy, prof. guilds, medical schools, docs, & research—even the FDA. So, press reports, web pages, & even academic literature can be unreliable.

Pharmaceutical Company Influence

It’s Everywhere, It’s Everywhere

Pharmaceutical Company Influence

It’s Everywhere, It’s Everywhere

Time, ed., & training to eval. clin. trial lit. or options.

Result is over-reliance on meds as a first-line tx & under-reliance on safer, comparably effective psychosocial options.

Inconsistent findings; method. problems, recall, selection bias, confounds; here most recent, sound, replicated findings

Time, ed., & training to eval. clin. trial lit. or options.

Result is over-reliance on meds as a first-line tx & under-reliance on safer, comparably effective psychosocial options.

Inconsistent findings; method. problems, recall, selection bias, confounds; here most recent, sound, replicated findings

Compounding the ProblemFront Line Physicians Don’t Have

Compounding the ProblemFront Line Physicians Don’t Have

First, The SSRI RCT LiteratureAre They Effective?

First, The SSRI RCT LiteratureAre They Effective?

Kirsch et al. (2008) & Fournier et al. (2010) meta-analytically examined available SSRI trials & found no differences between placebo & SSRIs, for mild, mod. or severe depression w/exception of the most distressed in severely depressed group.

The negligible advantage over placebo underlines the importance of their substantial adverse effects, including suicidal behavior and the birth defects to be discussed.

Kirsch et al. (2008) & Fournier et al. (2010) meta-analytically examined available SSRI trials & found no differences between placebo & SSRIs, for mild, mod. or severe depression w/exception of the most distressed in severely depressed group.

The negligible advantage over placebo underlines the importance of their substantial adverse effects, including suicidal behavior and the birth defects to be discussed.

Other Antidepressant DataOther Antidepressant Data

STAR*D: Largest SSRI trial: 108 of 4,041 who entered the trial remitted & stayed well to the FU period. 97% failed to remit, relapsed or dropped out

Rush et al. (2011): 1 SSRI produced same remission as 2 SSRIS at 12 weeks & 7 months but 2 produced sig. more adverse events.

STAR*D: Largest SSRI trial: 108 of 4,041 who entered the trial remitted & stayed well to the FU period. 97% failed to remit, relapsed or dropped out

Rush et al. (2011): 1 SSRI produced same remission as 2 SSRIS at 12 weeks & 7 months but 2 produced sig. more adverse events.

FDA Pregnancy Safety Ratings

A, B, C, D, & X

FDA Pregnancy Safety Ratings

A, B, C, D, & XCategory A: controlled studies show no

fetal risks associated with the drug; Category B: no evidence of risk in

humans, risks have been noted in animal studies;

Category C: risk cannot be ruled out; Category D: positive evidence of risk; andCategory X: contraindicated for use in

pregnancy. No SSRI has an A or B rating

Category A: controlled studies show no fetal risks associated with the drug;

Category B: no evidence of risk in humans, risks have been noted in animal studies;

Category C: risk cannot be ruled out; Category D: positive evidence of risk; andCategory X: contraindicated for use in

pregnancy. No SSRI has an A or B rating

Finland: Obstet Gynecol (6976;2011)

Cardiovascular Malformations

Finland: Obstet Gynecol (6976;2011)

Cardiovascular MalformationsFluoxetine: 2-fold

increase for ventricular septal defects; paroxetine: 4-fold for right ventricular outflow tract defects (0.5% for unexposed to .9% for SSRI to 2.1% for 2 SSRIs)

Fluoxetine: 2-fold increase for ventricular septal defects; paroxetine: 4-fold for right ventricular outflow tract defects (0.5% for unexposed to .9% for SSRI to 2.1% for 2 SSRIs)

SSRIs: Israel, Italy, GermanyBritish J. of Clin

Pharmacology(2008)

SSRIs: Israel, Italy, GermanyBritish J. of Clin

Pharmacology(2008)2191 pregnant women — 410 paroxetine

and 314 fluoxetine in the first trimester of pregnancy and 1467 controls.

2-fold increased risk in rate of congenital anomalies with SSRIs compared w/controls, cardiovascular anomalies most common.

Heart anomalies: 2.8% in the fluoxetine group, 2% in the paroxetine group, and 0.6% in the control group

2191 pregnant women — 410 paroxetine and 314 fluoxetine in the first trimester of pregnancy and 1467 controls.

2-fold increased risk in rate of congenital anomalies with SSRIs compared w/controls, cardiovascular anomalies most common.

Heart anomalies: 2.8% in the fluoxetine group, 2% in the paroxetine group, and 0.6% in the control group

More from the British Journal of Clinical

Pharmacology

More from the British Journal of Clinical

PharmacologyPrevious pregnancy

terminations (spontaneous abortion) were also higher in the fluoxetine & paroxetine groups compared with controls, with rates of 7.8%, 4.8%, and 2.8%. Birth weights were lower in the fluoxetine & paroxetine groups than control group.

Previous pregnancy terminations (spontaneous abortion) were also higher in the fluoxetine & paroxetine groups compared with controls, with rates of 7.8%, 4.8%, and 2.8%. Birth weights were lower in the fluoxetine & paroxetine groups than control group.

Prenatal Antidepressant Exposure Syndrome

Prenatal Antidepressant Exposure Syndrome

Exposure in the 3rd trimester related to embryotoxicity or poor neonatal adaptation: tremor, feeding difficulties, irritability, agitation, rigidity, and respiratory distress.

FDA and Health Canada warnings 

Exposure in the 3rd trimester related to embryotoxicity or poor neonatal adaptation: tremor, feeding difficulties, irritability, agitation, rigidity, and respiratory distress.

FDA and Health Canada warnings 

2006 FDA Warning2006 FDA Warning

Use of SSRIs past 20th week of pregnancy linked to a 6-fold increase in risk for persistent pulmonary hypertension (PPHN) in newborns

Use of SSRIs past 20th week of pregnancy linked to a 6-fold increase in risk for persistent pulmonary hypertension (PPHN) in newborns

Spontaneous AbortionCanadian Study: CMAJ

(5124;2010)

Spontaneous AbortionCanadian Study: CMAJ

(5124;2010) Use of SSRIs was

associated with a 68% increased risk of spontaneous abortion.

Use of more than one class of antidepressant doubled the risk of spontaneous abortion

Use of SSRIs was associated with a 68% increased risk of spontaneous abortion.

Use of more than one class of antidepressant doubled the risk of spontaneous abortion

Preterm Birth, Apgar, ICU Admits

Denmark Study: Arch of Ped & Adol Med

Preterm Birth, Apgar, ICU Admits

Denmark Study: Arch of Ped & Adol Med Infants of mothers

who took SSRIs during pregnancy at greater risk for preterm birth, a low 5-minute Apgar score, and admission to the neonatal intensive care unit.

Infants of mothers who took SSRIs during pregnancy at greater risk for preterm birth, a low 5-minute Apgar score, and admission to the neonatal intensive care unit.

Rates of AutismArch of Gen Psychiatry (1800;

2011)

Rates of AutismArch of Gen Psychiatry (1800;

2011) Autism: increased from

4 to 5 per 10,000 (1966) to almost 100 today.

Children whose mothers took an SSRI 1 yr prior to birth had 2X rate of ASD.

Children whose mothers took an SSRI during pregnancy had 3x the rate.

Autism: increased from 4 to 5 per 10,000 (1966) to almost 100 today.

Children whose mothers took an SSRI 1 yr prior to birth had 2X rate of ASD.

Children whose mothers took an SSRI during pregnancy had 3x the rate.

Findings Showing Increased Risk

What the “Experts” Say

Findings Showing Increased Risk

What the “Experts” Say “Need to balance the small

risks of SSRIs against those of no tx.”

“Only 3 times the risk. The general risk is 1%. So that means the risk is still just 3%.”

“No epidemiologic study can prove a risk, but if there is one, it appears to be low.”

“Important to interpret data in the context of the deleterious effects of untreated depression.”

“Need to balance the small risks of SSRIs against those of no tx.”

“Only 3 times the risk. The general risk is 1%. So that means the risk is still just 3%.”

“No epidemiologic study can prove a risk, but if there is one, it appears to be low.”

“Important to interpret data in the context of the deleterious effects of untreated depression.”

Taking a Closer LookThe Mantra of:

Taking a Closer LookThe Mantra of:

Meds pose only a small risk

Untreated depression has deleterious effects

Meds pose only a small risk

Untreated depression has deleterious effects

How Many Risks Are Enough?

How Many Risks Are Enough?

1. 2x the rate of cardiovascular malformations2. 6x the rate of persistent pulmonary

hypertension (and other withdrawal problems)3. 68% higher rate of spontaneous abortion4. Significantly more preterm births, lower Apgar

scores, and ICU admissions5. 2 or 3x the rate of autism6. Gestational hypertension: Over 2x the risk (9 v.

19%)7. Combined with the lack of efficacy and general

adverse effect package of SSRIs

1. 2x the rate of cardiovascular malformations2. 6x the rate of persistent pulmonary

hypertension (and other withdrawal problems)3. 68% higher rate of spontaneous abortion4. Significantly more preterm births, lower Apgar

scores, and ICU admissions5. 2 or 3x the rate of autism6. Gestational hypertension: Over 2x the risk (9 v.

19%)7. Combined with the lack of efficacy and general

adverse effect package of SSRIs

The Cumulative Risk Is Significant

The Myth of Untreated Depression

Underlying Illness, not the SSRIs

The Myth of Untreated Depression

Underlying Illness, not the SSRIs“Treated depression” doesn’t yield good results in RCTs

3 studies above compared depressed women who used SSRIs v. depressed women who didn’t: The Denmark, Canadian, and US studies found no effects of “untreated depression” on the fetus or newborn.

“Treated depression” doesn’t yield good results in RCTs

3 studies above compared depressed women who used SSRIs v. depressed women who didn’t: The Denmark, Canadian, and US studies found no effects of “untreated depression” on the fetus or newborn.

Recent Meta-Analytic Study Looked at PRB,

LBW, IUGR

Recent Meta-Analytic Study Looked at PRB,

LBW, IUGRDepression ??; 2/3 didn’t

control for SSRI useDepressed women from

US middle class or from a social democracy did not have birth defects; only impoverished countries or poor in the US; much stronger argument re poverty than untreated depression

Depression ??; 2/3 didn’t control for SSRI use

Depressed women from US middle class or from a social democracy did not have birth defects; only impoverished countries or poor in the US; much stronger argument re poverty than untreated depression

The Evidence Warrants A Serious Look

& Changes in Prescribing Practices

The Evidence Warrants A Serious Look

& Changes in Prescribing PracticesWe warn about alcohol & cigarettes, but how much evidence do we need to warn about psychiatric medications?

We warn about alcohol & cigarettes, but how much evidence do we need to warn about psychiatric medications?

Psychosocial Options First Find Alternatives in Your Area

Psychosocial Options First Find Alternatives in Your Area

Alternatives should be discussed: Stress reduction techniques, support groups, psychotherapy, reducing work hours, familial, Church, & community support.

Many women express concerns about medication during pregnancy & physicians must offer alternatives

Alternatives should be discussed: Stress reduction techniques, support groups, psychotherapy, reducing work hours, familial, Church, & community support.

Many women express concerns about medication during pregnancy & physicians must offer alternatives

In the Case of DepressionPsychological Treatments in

RCTs

In the Case of DepressionPsychological Treatments in

RCTsAre as effective as

medication in the short run with more durable benefits in the long run, even if the depression is severe

Although combined treatments are touted as the best option, they are not better than psychotherapy alone over the long term but they have better results than medication alone

Are as effective as medication in the short run with more durable benefits in the long run, even if the depression is severe

Although combined treatments are touted as the best option, they are not better than psychotherapy alone over the long term but they have better results than medication alone

A Call for A Higher Standard of Care

Duncan & Antonuccio (2011)

A Call for A Higher Standard of Care

Duncan & Antonuccio (2011)1). Informed consent and a

risk/benefit analysis2). Psychosocial intervention first—find alternatives3). Avoid polypharmacy or other

non- empirically supported

practices4). Monitor treatment response

with patient rated measures 5). Making Data Accessible6). Separate industry influence

from science and practice

1). Informed consent and a risk/benefit analysis

2). Psychosocial intervention first—find alternatives3). Avoid polypharmacy or other

non- empirically supported

practices4). Monitor treatment response

with patient rated measures 5). Making Data Accessible6). Separate industry influence

from science and practice

Pope Benedict XVI, Nov., 2006

Pope Benedict XVI, Nov., 2006

“Scientific predictability also raises the question of the scientists’ ethical responsibilities. His conclusions must be guided by respect for the truth & honest acknowledgement of both the accuracy & the inevitable limitations of the scientific method. Certainly this means avoiding needlessly alarming predictions when these are not supported by sufficient data or exceeds science’s actual ability to predict. But it also means avoiding the opposite, namely a silence born of fear, in the face of genuine problems. The influence of scientists in shaping public opinion is too important to be undermined by undue haste or the pursuit of superficial publicity.”

“Scientific predictability also raises the question of the scientists’ ethical responsibilities. His conclusions must be guided by respect for the truth & honest acknowledgement of both the accuracy & the inevitable limitations of the scientific method. Certainly this means avoiding needlessly alarming predictions when these are not supported by sufficient data or exceeds science’s actual ability to predict. But it also means avoiding the opposite, namely a silence born of fear, in the face of genuine problems. The influence of scientists in shaping public opinion is too important to be undermined by undue haste or the pursuit of superficial publicity.”

Conclusions The Evidence Speaks the Truth

Conclusions The Evidence Speaks the Truth

When clinical trials are examined & risks considered, the evidence does not support SSRIs as a first treatment for pregnant women.

Knowing that there is no compelling evidence to medicate, providers must discuss the risks/benefits & alternatives: Church, community, counseling to help women make choices that honor values, culture, & spirituality.

When clinical trials are examined & risks considered, the evidence does not support SSRIs as a first treatment for pregnant women.

Knowing that there is no compelling evidence to medicate, providers must discuss the risks/benefits & alternatives: Church, community, counseling to help women make choices that honor values, culture, & spirituality.

Bottom Line:

Look at the

evidence

yourself and

draw your own

conclusions

The ChurchIn Addition to Spiritual

Leadership

The ChurchIn Addition to Spiritual

LeadershipHas a rich history of

benefiting humanity, comforting the frail and disenfranchised, protecting the sanctity of human life, and strengthening families. The Church may be the only power on earth that can counter the forces of corporate greed that have no moral or ethical conscience.

Has a rich history of benefiting humanity, comforting the frail and disenfranchised, protecting the sanctity of human life, and strengthening families. The Church may be the only power on earth that can counter the forces of corporate greed that have no moral or ethical conscience.