PSYCHIATRIC DISORDERS IN PREGNANCY

Prepared by JINI J, M.Sc(N)

INTRODUCTION
Psychiatric disorders particularly mood & anxiety disorders have the highest prevalence in women during the childbearing years. Some women experience the onset of psychiatric symptoms for the first time during pregnancy, while others are already being treated for a psychiatric disorder.

PSYCHIATRIC DISORDERS
Anxiety Bipolar disorder Depression Eating disorder Schizophrenia Substance abuse

Live Births and Fertility Rates in U.S.

Approximately 50% are unplanned pregnancies At least 500,000 pregnancies each year are associated with psychiatric illness

CDC: Births: Preliminary Data 2006; National Vital Statistics Report. Volume 57, Number 7, December 2007.

Myth Busters
Pregnancy is a time of emotional wellbeing Category B is a safer category in pregnancy There is a specific algorithm for the treatment of pregnant patients It is best to stop psychotropic medications prior to conception It is best to taper psychotropic medications prior to delivery

Obstacles to Recognition and Treatment of Perinatal psychiatric Disorders

High expectations of joy & happiness with new baby: cognitive dissonance if dysphoric symptoms arise. Attribution of dysphoria to stress, not assessing hallmark symptoms. Self blame. Lack of knowledge about mood and anxiety disorders. Critical role of antenatal education.

Specific concerns regarding psychiatric disorders in pregnancy

Teratogenesis Toxicity to the newborn Neuro behavioural sequelae Risk of no treatment Risk of medication discontinuation

ANXIETY AND PREGNANCY

 Certain amount of stress and anxiety during pregnancy may be inevitable, there is growing evidence that high levels can affect children long after birth.

Incidence
6% of pregnant women are affected Sometimes anxiety may occur along with depression.

Causes
Worries about Whether the baby is healthy How the baby will change the relationship and life Whether she is truly upto the task of parenthood

Risk factors
Constant worry Feeling something bad is going to happen Disturbance of sleep and thought Physical symptoms like dizziness, hot flushes & nausea Personal and family history of anxiety Previous perinatal depression or anxiety Thyroid imbalance

Symptoms
Shortness of breath Chest pain Dizziness Heart palpitations Numbness Tingling in the extremities

Effects of Pregnancy on the Natural Course of Anxiety Disorders

Panic disorder: Increased risk of recurrence or intensification postpartum. Obsessive compulsive disorder: Many women with OCD (perhaps around 40%) have initial onset of symptoms during pregnancy or the postpartum period.

Complications
Miscarriage Preterm delivery Low birth weight babies

Management
Preconception
Anxiolytic medication should be reduced or stopped. Reduction should be combined with alternative non pharmacological therapy like supportive and cognitive therapy.

Antenatal
Anxiolytic should be avoided If essential minimum dose for short period First trimester anxiety can be managed with supportive care and re-assurance Drug therapy is given for severe cases.

Postnatal
Observe the mother for deterioration in symptoms Observe the neonate for fetal exposure to drugs in the third trimester, or during parturition, is associated with a neonatal withdrawal syndrome.

Assessing the Safety of Psychotropic Medications in Pregnancy

Prospective, double blind studies drug trials are unethical. Therefore, we are dependent on information from case reports, retrospective chart reviews, animal toxicology studies. Best summaries to date of this body of evidence: Wisner et al., (2002) NEJM 347: 194-199; Newport et al. (2004) The APA Textbook of Psychopharmacology, 3rd Edition

Drug management
A)Benzodiazepines Ten fold increase of cleft palate in the fetus during the first trimester exposure. But research founded that no relationship between fetal exposure to BZ and cleft palate.

 B)Antihistamines Promethazine is a simple hypnotic with anxiolytic properties Bromopheniramine, antihistamines could be considered as simple hypnotics in pregnant women

 C)Other hypnotics Non benzodiazepine agents such as ZOPICLONE and ZOLPIDEM are used But occasional use is considered as safe.

Anxiolytics During Pregnancy/Lactation

Diazepam, other benzos: initial reports that 1st trimester exposure to diazepam, other benzos increase risk of oral clefts not substantiated. Clonazepam: lowest teratogenicity of all benzos in animal studies. No clear teratogenicity when used in pregnant epileptics. Lorazepam: safe track record. Limited milk penetration. Low-medium doses considered reasonably safe. Risks: infant sedation, hypotonicity, postnatal withdrawal. Alprazolam: some evidence that exposure may increase oral cleft risk 12 times (0.06% to 0.7%).

Non pharmacological measures

DEPRESSION AND PREGNANCY

Introduction
Depression is more than just feeling blue or down in the dumps for a few days. Its serious illness that involves the brain. It interfere with day to day life and routines It also produce sad, anxious and the empty feeling.

Incidence
All pregnant women should expect some mood variation in pregnancy 10% of all pregnant women may get antenatal depression.

Risk factors
Personal or family history of depression Relationship difficulties Fertility treatment Previous pregnancy loss Problems with pregnancy Stressful life events Past history of abuse Lack of social support Financial difficulties Problems with pregnancy

Diagnosing Perinatal Depression: Hallmark Psychological Symptoms

Depressive mood, sadness, tearfulness. Diminished interest or pleasure in most activities (especially in taking care of the baby). Feelings of worthlessness or inappropriate guilt (especially about being an inadequate mother). Recurrent thoughts of death or suicide. Edinburgh Postnatal Depression Scale: Cox et al.,
1987, Br J Psychiatry 150: 782-6.

Symptoms
Inability to concentrate & remember Difficulty in making decision Anxiety about pregnancy and becoming parents Feeling emotionally numb Extreme irritability Sleep problems Extreme or unending fatigue A desire to eat at all time or not wanting to eat at all

 Weight loss or weight gain not related to pregnancy Loss of interest in sex Nothing feels enjoyable or fun including pregnancy Feeling like a failure or guilt Persistent sad Thoughts of death or suicide

Assessment of depression

Complications
For mother Poor eating Not gain enough weight Have trouble sleeping Miss prenatal visits Not follow medical instructions Use harmful substances, like tobacco, alcohol or illness

For baby Problem during pregnancy and delivery Low birth weight babies Premature birth

Management

Antidepressant Use in Pregnancy

Recent studies estimate up to 9% of pregnant women may take an SSRI during pregnancy Several studies have also shown an increase in antidepressant use SSRIs accounted for the largest increase

SSRIs in Pregnancy
No major teratogenic risk associated with SSRI use Possible increase in cardiac defects with first trimester exposure to paroxetine Adverse perinatal outcomes: conflicting data Persistent pulmonary hypertension Possible increase in spontaneous abortion No significant developmental delay in children

Cohen L. Treatment of Bipolar Disorder During Pregnancy. J. Clinical Psychiatry 68 (9), 2007: 4-9.

Guidelines for Treatment of Major Depression During Pregnancy/Lactation

SSRIs (fluoxetine, sertraline) or secondary amine tricyclic antidepressants (desipramine, nortriptyline) during pregnancy or lactation. Buproprion is probably reasonably safe. Monitor TCA blood levels; increase dose as necessary as pregnancy advances, cut back dose at parturition.

Late 3rd trimester exposure

Neonatal Behavioral Syndrome Symptoms include:
 Jitteriness  Tachypnea  Tremulousness  Hypertonia  Restlessness

Difficult to differentiate reported adverse outcomes related to:

 Antidepressant exposure  Antidepressant withdrawal  Maternal depression and anxiety

A Multisite Retrospective Study

118,935 deliveries 2001-2005, 6.6% women took antidepressants Antidepressant use increased from 2% deliveries in 1996 to 7.6% deliveries in 2005 SSRI use increased from 1.5% in 1996 to 6.4% in 2004
Andrade S et al. Use of antidepressant medications during pregnancy: a multisite study. American Journal of Obstetrics and Gynecology. Feb. 2008

SSRIs and Persistent Pulmonary Hypertension

Cohort Study: SSRIs in late pregnancy may be a risk factor for PPHN (Chambers et al 1996) Case-Control Study: (Chambers et al 2006)
14 infants were exposed to an SSRI after the 20th week of gestation Retrospective design Absolute risk: 7/1000 women Based on this study, in April 2006 the FDA required a label change to include SSRIs increasing the risk for PPHN
Chambers C, Hernandez-Diaz S, Van-Marter L et al. Selective Serotonin-Reuptake Inhibitors and Risk of Persistent Pulmonary Hypertension of the Newborn. N Engl J Med. Vol 354:6 579-587, February 9, 2006.

Paxil and Cardiac Defects

Multiple studies show no increased risk of cardiac defects with Paxil or other antidepressants Meta-analysis (Koren et al. 2007)
 Increased risk for cardiac malformation  Women using antidepressants had higher numbers of echocardiograms, amniocentesis and ultrasounds  Women on paroxetine used the drug for anxiety and panic

Epidemiologic Study (Koren et al. 2008)

 1,174 unpublished cases and 2,061 cases from published database studies  The rate of cardiovascular defect falls within the normal rate in the general population
Bar-Oz, Einarson T, Koren G et al. Clinical Therapeutics. 2007: 29: 918-926. Einarson A, Pistelli A, Koren G. AJP. 1008: 1-4. April, 2008

Depression Relapse in Pregnancy: Cohen et al. 2006:

43% of the women experienced relapse during pregnancy 26% who maintained medication relapsed

68% who discontinued medication relapsed

Cohen L, Altshuler L, Harlow B et al. Relapse of Major Depression During Pregnancy in Women Who Maintain or Discontinue Antidepressant Treatment. JAMA Vol 295 (5),: 499-507, 2006.

Other Antidepressants
Venlafaxine Trazodone Mirtazapine Duloxetine Bupropion MAOI inhibitors are avoided in pregnancy

Tricyclic Antidepressants
No major risk for malformations Desipramine and nortriptyline preferred less anticholinergic activity Perinatal syndromes described in infants
Anticholinergic effects are transient (bowel obstruction, urinary retention)

Withdrawal Syndrome No long-term neurobehavioral effects

Other Treatment Options

Cognitive Behavioral Therapy Interpersonal Therapy Group Therapy Light Therapy

Electroconvulsive Therapy
Safety well documented over 50 years Organ Dysgenesis
 Occasional reports of malformations but no direct causal link to ECT

Intrauterine Growth Defects/Neonatal Toxicity

 None

Neurobehavioral Teratogenicity
 Few case reports - developmental delays or MR  No direct causal link to ECT

Seizure threshold
 decreased by estrogen, and increased by progesterone

Recommendations for Antidepressant Treatment in Pregnant Women

Psychotherapy is first line for mild-moderate depression Psychotherapy + antidepressant recommended for moderate to severe depression Individualized risk-benefit analysis No Rx of antidepressant treatment: SSRI antidepressant considered first-line Successful history of antidepressant treatment: data should be reviewed with mom, and considered first line L, Moline M et al. Treatment of Depression in Women: A Summary of the Expert Consensus Guidelines. Altshuler L, Cohen,
Journal of Psychiatric Press: 185-208, May, 2001.

Recommendations continued
ECT for psychotic depression Review all risks and benefits of treatment Moms should be monitored carefully for increased depression, mania or psychosis Dosages may need to be adjusted Goal is monotherapy and minimal effective dosage
Altshuler L, Cohen, L, Moline M et al. Treatment of Depression in Women: A Summary of the Expert Consensus Guidelines. Journal of Psychiatric Press: 185-208, May, 2001

Complementary and Alternative Medications for Perinatal Depression

Omega-3-fatty acids: general data support use in pregnancy and postpartum S-adenosyl-methionine: Some efficacy in reducing depression Folate: some evidence to support augmentation for depression St. Johns Wort- some evidence of efficacypossible drug interactions
Freeman, M. Complementary and Alternative Medicine for Perinatal Depression. Journal of Affective Disorders, 2008.

CAM continued
Bright light therapy: evidence supports potential use in perinatal and postpartum Acupuncture: caution advised in pregnant women Massage: some efficacy in pregnancy Exercise: appears to have antidepressant effects

Proposed Treatment Algorithm

Illness Severity Risk of Untreated Illness Risk of Relapse Risk to Fetus

Goal is Sustained Healthy Mental State

Lowest Effective Dosage

Monotherapy

Consult!

BIPOLAR DISORDER AND PREGNANCY

Introduction
Pregnancy is a very risky period for women with bipolar disorder are often discouraged from having children Many women with bipolar disorder become pregnant or plan to have children at some points in their lives.

Incidence
According to National Alliance on Mental Illness(NAMI) Pregnant women and new moms with bipolar disorder are 7 times more likely to be hospitalized 2 times more likely to have recurrent episode compared with non pregnant The risk is about 10 20% 67-82% will relapse within 3-6 months after childbirth

Risk factors
Childhood psychiatric problems Hormonal fluctuations during pregnancy can aggravate symptoms

Symptoms

Guidelines for Treatment of Mania During Pregnancy/Lactation

First trimester: Haloperidol for psychosis, clonazepam for agitation; if mood stabilizer is necessary, lithium may be first choice. ECT. Second/Third trimester/Postpartum: Lithium or anticonvulsants, haloperidol and/or clonazepam if truly needed. Continue treatment postpartum if no obstetric complications. Follow breast-fed infants closely.

Guidelines for Treatment of Mania During Pregnancy/Lactation-cont

Monitor blood levels of mood stabilizers as pregnancy advances and increase doses to maintain effective concentrations. At parturition, decrease doses of mood stabilizers by approximately one third to prevent levels from rising into the toxic range.

Management
Lithium before delivery or within 48hrs of delivery to reduce the risk of relapse Close monitoring to prevent neonatal toxicity First generation antipsychotics like haldol and thorazine are safe than anticonvulsants auch as depakote & tegretol

Alternative management
ECT Familial support Massage Acupuncture Yoga

EATING DISORDER AND PREGNANCY

Introduction
Eating disorder are just as common during pregnancy as they are in non-pregnant women

Incidence
20% of pregnant women Bulimia and binge eating disorder being the most common during pregnant especially in Western cultures.

Relationship between eating disorder and pregnancy

Causes
Previous eating disorder before pregnancy Lower education Lower income

Effects on the mother

Poor nutrition Dehydration Cardiac irregularities Gestational diabetes Severe depression during pregnancy Premature births Labour complications Postpartum depression Difficulties in nursing

Effects on the baby

Poor development Premature birth Low birth weight for age Respiratory distress Other perinatal complications Feeding difficulties Liver disorder Cerebral palsy

Cleft palate Blindness Preterm labour Low APGAR score Miscarriage still birth

Prevention

Management
Counselling Cognitive behaviour therapy(CBT)

Alternative and complementary therapy

Acupuncture Aromatherapy Naturopathy

SCHIZOPHRENIA AND PREGNANCY

Definition
Schizophrenia is a psychotic disorder characterized by loss of contact with the environment, by noticeable deterioration in the level of functioning in everyday life, and by disintegration of personality expressed as disorder of feeling, thought. It is also called as DEMENTIA PRAECOX.

Risk factors
Maternal infections and flu in pregnancy Lead, alcohol and other toxic exposure Use of painkillers in pregnancy liked to be higher risk Maternal stress during prgnancy Excess body weight during pregnancy Complications during pregnancy and labour Celiac disease (wheat allergy)may slightly increase the risk.

Clinical features
Delusion Hallucination Disintegration of the process of thinking Lack of insight

Complications
Side effects of anti-psychotic drugs during pregnancy Inability to maintain pregnancy Aggravation of previously controlled schizophrenia Offspring are at increasing risk of developing the condition

Medical management
Antipsychotic Chlorpromazine(thorazine, largactil) Fluphenazine(prolixin)  These may impair fertility Newer antipsychotic Olanzapine risperidone Doses can be reduced during third trimester to reduce the side effects.

Psychosocial treatment
Psycho education Group psychotherapy Family therapy Milieu therapy Psychosocial rehabilitation Individual psychotherapy

Newer findings
Schizophrenia and estrogen and pregnancy Schizophrenia and smoking and pregnancy

Managing Pregnancy in Women Who Require Chronic Psychotropic Medication

Emphasize the importance of birth control and planning pregnancies. Stop meds during 1st trimester, if feasible. Plan A: If possible, taper and stop medication prior to attempts to conceive, e.g. at the beginning of a menstrual cycle. Plan B: Detect pregnancy as early as possible (2 wks with OTC pregnancy tests), then taper/stop medication.

Managing Pregnancy in Women Who Require Chronic Psychotropics-cont

If stability requires 1st trimester medication, consider switching to a less risky medication that could reasonably prevent relapse (e.g., from anticonvulsant to lithium or haloperidol). If a mood stabilizer or lithium is necessary during the 1st trimester, discuss ultrasound examination of the fetus at 16-18 wks of pregnancy and how malformations might be handled (abortion?) before conception.

Managing Pregnancy in Women Who Require Chronic Psychotropics-cont

To diminish the period off of or on less than optimal medication, resuming most psychotropics after the 1st trimester (lithium, some anticonvulsants?) is reasonably safe. Risk of postpartum relapse in women with history of recurrent mood disorders is diminished by resuming medication immediately postpartum or even shortly prepartum.

SUBSTANCE ABUSE AND PREGNANCY

Dangerous drugs
Alcohol Cocaine Heroin Amphetamines Tobacco Marijuana

Effects of drug exposure

Potential Risks of Treatment with Psychiatric Medications

Malformations. Behavioral teratogenicity. Drug effects on the newborn- toxicity, withdrawal. Blood volume changes: Drug levels shift into the sub-therapeutic range during pregnancy or toxic range postpartum.

Potential Risks of Not Treating With Psychiatric Medications

Anxiety , other untreated psychiatric disorders during pregnancy are associated with poor obstetric outcomes. In utero stress retards fetal growth, may disrupt normal behavioral development. Children of mentally ill mothers have more medical, psychological, and cognitive problems. Increased risk of recurrence and treatment resistance of illness.

Mothers eat healthy food, exercise wisely and avoid harmful substance!!! You are protected and you are protecting your unborn