MERRILL!SPARAGO,!MD! · when!a!patient!has!a! perinatal!mood!disorder (pmd)! •...

DIAGNOSTIC & TREATMENT CONSIDERATIONS IN

PERINATAL MOOD DISORDERS

MERRILL SPARAGO, MD

LECTURE OBJECTIVES

•  DESCRIBE THE PROCESS OF DIAGNOSTIC ASSESSMENT IN EVALUATING PERINATAL MOOD/ANXIETY DISORDERS (PMDS)

•  PROVIDE A FRAMEWORK FOR UNDERDSTANDING THE USE OF MEDICATIONS IN PMDS

•  DISCUSS PHARMACOLOGIC TREATMENT OF PMDS •  SORT THROUGH THE CONFUING AND CONTRADICTORY

LITERATURE ABOUT PHARMACOTHERAPY IN PREGNANCY/POSTPARTUM

WHEN A PATIENT HAS A PERINATAL MOOD DISORDER

(PMD) •  THERE IS NO NON EXPOSED GROUP IN TREATING PMD’S….ZACHARY STOWE, M.D. •  PATIENTS AND THE DEVELOPING FETUS OR NEWBORN ARE EITHER EXPOSED TO THE MORBIDITY AND MORTALITY OF THE ILLNESS, THE TREATMENT, OR BOTH.

WHEN TREATING A PERINATAL MOOD DISORDER (PMD)

•  THE BEST TREATMENT STRATEGY IS TO MINIMIZE OR ELIMINATE ONE OF THE EXPOSURES WHENEVER POSSIBLE

•  MEDICATIONS ARE USED ONLY WHEN OTHER TREATMENT OPTIONS SUCH AS THERAPY ARE NOT EFFECTIVE OR UNAVAILABLE/UNDESIRED BY THE PATIENT.

•  MEDICATIONS SHOULD IDEALLY BE USED IN CONJUNCTION WITH THERAPY.

•  WE TREAT WITH THE LOWEST POSSIBLE DOSE BUT I BELIEVE IF YOU ARE GOING TO TREAT, THEN TREAT WITH THE GOAL OF APPROACING/ACHIEVING REMISSION TO AVOID ONE OF THE EXPOSURES.

THE TREATMENT TEAM PERINATAL MOOD DISORDERS (PMD’S)

•  ANALOGY TO ONCOLOGY: TREATING PERINATAL MOOD DISORDERS IS A TEAM EFFORT.

•  WHENEVER POSSIBLE THE TEAM SHOULD INCLUDE AN EXPERT IN PMD’S AS WOULD ONCOLOGIC ILLNESS

•  OUR JOB IS TO INCREASE THE NUMBER OF PROVIDERS •  THE PROBLEM IS REFERRALS: YOU CAN BECOME PART OF THE

SOLUTION

THE OBSTETRICIAN/PSYCHIATRIST AND PERINATAL MOOD DISORDERS (PMD’S)

•  TO ENSURE THE BEST OUTCOME FOR MOM, BABY, FAMILY AND PHYSICIAN A CONSULTATION WITH AN EXPERT IN PERINATAL MOOD DISORDERS (EVEN IF IT’S A CURBSIDE) SHOULD BE STRONGLY CONSIDERED

RISKS FACTORS ASSOCIATED WITH THE DEVELOPMENT OF PMD’S

•  HX MOOD, ANXIETY, PSYCHOTIC D/O. •  INFERTITLITY. •  UNPLANNED PREGNANCY. •  GESATATIONAL ABNORMALITIES. •  CONFLICTS IN RELATIONSHIP/POOR SOCIAL SUPPORT.

•  LOW BW/NEONATAL HEALTH PROBLEMS (PPD).

RISKS ASSOCIATED WITH PMD’S

•  MORBIDITY: POOR MATERNAL AND FETAL OUTCOMES

•  MOM: POOR WEIGHT GAIN, POOR SELF CARE/EATING HABITS, INCREASED TOB AND ETOH USE, INCREASED OBSTETRICAL INTERVENTIONS

•  FETUS: SGA, LBW, ALTERED CORTISOL RESPONSE, PRETERM BIRTH

RISKS ASSOCIATED WITH PMD’S

•  MORTALITY: SUICIDE/ABORTION SECONDARY TO INTOLERABLE PSYHCIATRIC SX; INFANTICIDE .4% IN POSTPARTUM PSYCHOSIS (PPP).

•  HOW ARE THEY MISSED: IS IT SHAME-‐ ARE PATIENT’S GIVING THEIR OB AN ACCURATE PSYCH HX?

•  NOT ALWAYS….

PMD’S: CONCEPTION AND PREGNANCY

•  INCIDENCE 12-‐20%. •  ANXIETY AND DEPRESSION CAN DECREASE CHANCE OF CONCEPTION.

•  THERE IS NOT CONVINCING EVIDENCE THAT TREATING DEPRESSION AND ANXIETY DURING CONCEPTION INHIBTS FERTILITY.

PMD’S: IS PREGNANCY PROTECTIVE?

NO!!!

PMD’S: IS PREGNANCY PROTECTIVE? DEPRESSION Cohen LS, JAMA Feb 2006

n=201 PROSPECTIVE STUDY OVERALL 43% OF WOMEN RELAPSED -‐ 21% RELAPSED WHO CONTINUED ANTIDEPRESSANTS -‐ 68% RELAPSED WHO D/C ANTIDEPRESSANTS

-‐ OVERALL 5X RISK OF MOOD EPISODE WHEN STOPPING TREATMENT

PMD’S: IS PREGNANCY PROTECTIVE? BIPOLAR DISORDER

Viguera AC, et.al. Am J Psych, Dec 2007 -‐ PROSPECTIVE STUDY -‐ OCCURNECE OF MOOD EPISODE DURING PREGNANCY 71% -‐ 2X INCREASE RISK OF MOOD EPISODE FOR WOMEN WHO

STOPPED THEIR RX. -‐ TIME TO RECURRENCE 4X SHORTER. -‐ ALMOST 50% RELAPSE IN 1ST TRIMESTER -‐ 5X INCREASE IN WEEKS SPENT ILL, MOSTLY DEPRESSED OR

MIXED -‐ 11X INCREASE IN TIME TO RECURRENCE RAPID D/C VS

TAPER. IN GENERAL PT’S ON LITHIUM FARED BETTER

-‐

PMD’S: IS PREGNANCY PROTECTIVE? BOTTOM LINE/WHAT CAN BE DONE

IF YOU ARE DEPRESSED IN PREGNANCY YOU WILL MOST LIKELY CONTINUE TO BE DEPRESSED IN PREGNANCY OR THE POSTPARTUM

PREGNANCY/DELIVERY DOES NOT CURE OR TREAT PERINATAL MOOD DISORDERS!!!!! HOSPITALIZATION RATES ARE 7X BASELINE RATE IN FIRST 30 DAYS POSTPARTUM

FOR PATIENT’S WITH A HISTORY OF MOOD/ANXIETY DISORDERS CLINICAL OUTCOMES CAN BE IMPROVED WITH PRECONCEPTION PLANNING (WHENEVER POSSIBLE) AND PARTNERSHIP WITH A PERINATAL MENTAL HEALTH SPECIALIST EVEN IF IT’S A CURBSIDE.

MY CELL IS 310-‐428-‐7700 .

PERINATAL MOOD DISORDERS PRIMARY DIFFERENTIAL

-‐  BABY BLUES -‐  DEPRESSION/MAJOR DEPRESSION/BIPOLAR DISORDER

-‐  POSTPARTUM DEPRESSION -‐  POSTPARTUM DEPRESSION WITH PSYCHOTIC FEATURES

-‐  POSTPARTUM PSYCHOSIS -‐  SCHIZOAFFECTIVE DISORDER

POSTPARTUM BLUES

-‐ INCIDENCE: 50-‐75% OF LIVE BIRTHS. -‐ PRESENTS 1ST WEEK PP. -‐ RESOLVES BY WEEK 2. -‐SX: OVERWHELMED, ANXIOUS, MOOD LABILITY, CRYING.

-‐SLEEP IS PRESERVED. -‐NO HOPELESSNES SI/HI/OBSESSIONS.

POSTPARTUM DEPRESSION (PPD)

-‐  12-‐20% OF LIVE BIRTHS

-‐  ETIOLOGY: UNKNOWN, RAPID SHIFT IN GONADAL STEROIDS, THYROID FUNCTION , CORTSIOL, PROLACTIN

-‐  PRESENTATION: ANYTIME FROM THE IMMEDIATE POSTPARTUM TO A YEAR OUT (EVEN FURTHER……)

-‐  ANXIOUS DEPRESSION, INSOMNIA, HOPELESSNESS, FEARS OF BEING A BAD MOTHER/HARM COMING TO THE BABY, GUILT

-‐  40-‐60% HAVE OBSESSIVE THOUGHTS: INTRUSIVE REPETITVE EGO-‐DSYTONIC THOUGHTS INCLUDING HARMING THE BABY;

-‐  REALITY TESTING AND JUDGMENT INTACT

ACOG SCREEN •  THE AMERICAN COLLEGE OF OBSTETRICIANS AND

GYNECOLOGISTS (ACOG) RECOMMENDS A TIMELY SCREENING METHOD-‐ ASKING THE FOLLOWING QUESTIONS: –  (A) OVER THE PAST 2 WEEKS, HAVE YOU EVER FELT DOWN, DEPRESSED, OR HOPELESS?

–  (B) OVER THE PAST 2 WEEKS, HAVE YOU FELT LITTLE INTEREST OR PLEASURE IN DOING THINGS?

MY POSTPARTUM TRIPLE SCREEN

1) “CAN YOU SLEEP WHEN THE BABY IS SLEEPING/HAVE YOU SLEPT?”

2) “ARE YOU FEELING HOPELESS, HAVING THOUGHTS OF HARMING YOURSELF OR OTHERS INCLUDING THE BABY?”

3) “WHAT WOULD STOP YOU FROM ACTING ON THOSE THOUGHTS?” IF ANY OF THESE ARE “YES” OR “I DON’T KNOW” IT IS NOT THE BABY BLUES AND

THERE NEEDS TO BE A CLINICAL INTERVENTION

PPD TREATMENT OPTIONS

#1 RULE MOM MUST SLEEP!!!!! PSYCHOTHERAPY

INTERPERSONAL (IPT); COGNITIVE BEHAVIORAL (CBT) PSYCHODYNAMIC/INSIGHT ORIENTED GROUP/FAMILY *MOST SUCCESSFUL OUTCOMES WITH A COMBINATION OF MEDICATION AND THERAPY

PPD PHARMACOTHERAPY

-‐ SSRIS (FLUOXETINE, PAROXETINE, CITALOPRAM, S-‐CITALOPRAM, SETRALINE, FLUVOXAMINE) – PRIMARY TREATMENT -‐ SNRIS (VENLAFAXINE, DULOXETINE) MAY BE EFFECTIVE BENZODIAZEPINES: INSOMNIA/ANXIETY

-‐ PPD WITH PSYCHOTIC FEATURES OR SEVERE

REFRACTORY DEPRESSIVE SYMPTOMS: ATYPICAL ANTIPSYCHOTIC (OLANZAPINE, RISPERIDONE, ARIPIPRAZOLE, QUETIAPINE , ZIPRASIDONE)

**** MORE ON MEDS TO COME****

POSTPARTUM OBSESSIVE/COMPULSIVE DISORDER (PPOCD)

-‐ 2-‐3%; MORE COMMON IN PRIMIPAROUS WOMEN -‐ PEUPERIUM IS A RISK FACTOR FOR NEW ONSET OCD SYMPTOMS OCCUR IN THE EARLY POSTPARTUM, OFTEN COMORBID PPD

-‐ ETIOLOGY – UNKNOWN, ALTERATIONS IN GONADAL STEROIDS AND INFLUENCE ON NEUROTRANSMITTER SYSTEMS (5-‐HT; DA) -‐ AVOIDANT/OCPD MAY BE A RISK FACTOR*

-‐ COURSE – CHRONIC AND OFTEN ACCOMPANIED BY DEPRESSION AND FEELING OF “GOING CRAZY”

*FARUK ET. AL., 2007

PP OCD CORE SYMTPOMS OBSESSIONS AND COMPULSIONS

OBSESSIONS: INTRUSIVE, UNWANTED, EGO DYSTONIC, REPETITIVE THOUGHTS THAT CAUSE SIGNIFICANT DISTRESS.

*NOT RUMINATIONS ABOUT DAILY LIFE STRESSORS. MOST COMMON: HARMING THE BABY, CONTAMINATION,

SYMMETRY. COMPULSIONS: REPETITIVE BEHAVIORS DIRECTED AT DECREASING

ANXIETY OF OBSESSIONS BEHAVIORAL (OBSERVABLE) AVOIDANCE, HIDING OBJECTS, WASHING/CLEANING OR ORGANIZING MENTAL (INOBSERVABLE) COUNTING, UNDOING, RATIONALIZING, LOGIC

PP OCD TREATMENT

-‐ PATIENT EDUCATION: NOT AT INCREASED RISK OF HARMING THE BABY (COMORBID DEPRESSION MAY INCREASE RISK OF SELF HARM.

-‐ PSYCHOTHERAPY: CBT (PREFERRED) INTERPERSONAL THERAPY (DEPRESSION) GROUP FAMILY

POSTPARTUM OCD PHARMACOTHERAPY

-‐ SSRIS (FLUOXETINE, PAROXETINE, CITALOPRAM, S-‐CITALOPRAM, SETRALINE, FLUVOXAMINE) – PRIMARY TREATMENT, OFTEN NEED HIGHER DOSES THAN FOR DEPRESSION -‐ SNRIS (VENLAFAXINE, DULOXETINE) MAY BE EFFECTIVE BENZODIAZEPINES: INSOMNIA/ANXIETY

-‐ ATYPICAL ANTIPSYCHOTIC (OLANZAPINE, RISPERIDONE, ARIPIPRAZOLE, QUETIAPINE , ZIPRASIDONE)

-‐ GLUTAMATE ANTAGONISTS (GALANTAMINE)

POSTPARTUM PSYCHOSIS (PPP)

-‐ EPIDEMIOLOGY -‐ .1% 100X HIGHER IN WOMEN WITH BIPOLAR DISORDER (10%) .

-‐ PPP: CONSIDERED A MANIFESTATION OF BIPOLAR DISORDER UNTIL PROVEN OTHERWISE

-‐ ALSO INCREASED RISK IN PATIENTS WITH SCHIZOAFFECTIVE DISORDER, SCHIZOPHRENIA

-‐ ETIOLOGY – MAY BE RELATED TO PROFOUND DROP IN ESTROGEN/PROGESTERONE WITH CHILD BIRTH.

GENETIC FACTORS – CHROMOSOME 16P13* *JONES AND CRADDOCK, 2007

POSTPARTUM PSYCHOSIS CLINICAL PRESENTATION

CORE SYMPTOMS INCLUDE: MOOD LABILITY DELUSIONS – FIXED FALSE BELIEFS HALLUCINATIONS – PERCEPTUAL DISTURBANCES

PERCEIVED AS COMING EXTERNALLY RATHER THAN INTERNALLY

THOUGHT DISORDER/DELIRIUM – “COGNITIVE DISORGANIZATION PSYCHOSIS”*

APPROXIMATELY .4% OF WOMEN WITH PPP COMMIT INFANTICIDE *

*WISNER ET. AL., 1994

POSTPARTUM PSYCHOSIS CLINICAL PRESENTATION (CONT.)

NO INSIGHT INTO THE NATURE OF THE SYMPTOMS EGO SYNTONIC -‐ BELIEVED TO BE IN LINE WITH REALITY (THIS DISTINGUISHES DIAGNOSIS FROM OCD) OFTEN PRESENTS LIKE A DELIRIUM

WAXING AND WANING OF SYMPTOMS ALTERED LEVEL OF AROUSAL ORIENTATION/SENSORIUM IMPAIRED CONFUSION MEMORY LOSS BIZARRE BEHAVIOR CAN FLUCTUATE WITH MOMENTS OF LUCENCY

POSTPARTUM PSYCHOSIS DELUSIONAL CONTENT

-‐ RELIGIOUS DELUSIONS – ANDREA YATES -‐ DELUSIONS OF CONTROL -‐ GRANDIOSE DELUSIONS -‐ PARANOID -‐ BIZARRE CONTENT

-‐ COMMAND HALLUCINATIONS – INCREASED RISK OF INFANTIDCIDE

POSTPARTUM PSYCHOSIS (PPP) A MEDICAL EMERGENCY*

IF THE DIAGNOSIS IS POSTPARTUM PSYCHOSIS, YOU MUST TAKE IMMEDIATE AND ALL NECESSARY ACTION TO MINIMIZE RISK OF SELF HARM/INFANTICIDE:

THEREFORE: IMMEDIATE HOSPITALIZATION IS THE TREATMENT FOR PPP. FAMILY WATCH IS NOT SUFFICENT

PHARMACOTHERAPY MOOD STABILIZERS, ANTI-‐PSYCHOTICS, SEDATIVES, ECT

*MEG SPINELLI, M.D.

WHAT’S AFTER THE DIAGNOSIS? WHEN MEDICATION IS NEEDED

•  DETERMINING WHETHER A MEDICATION IS NEEDED IS ALWAYS DONE ON A CASE BY CASE BASIS

•  AN EVALUATION OF PERINATAL MOOD DISORDERS MUST INCLUDE A COMPLETE HISTORY OF THE ILLNESS INCLUDING ALL MEDICATIONS THAT HAVE BEEN TRIED, HAVE FAILED, OR HAVE BEEN SUCCESFUL.

•  ILLNESS SEVERITY, HOSPITALIZATIONS, AGE OF ONSET, NUMBER OF EPSIODES, CORE SYMTPOMS, HERALD SYMPTOMS, H/O PERINATAL MOOD DIORDERS /PMDD.

•  RESPONSIVENESS OR LACK THEREOF TO OTHER LESS RISKY FORMS OF TREATMENT

•  PLANNED PREGANCY OR UNPLANNED PREGNACY, COURSE OF PREGNANCY, DELIVERY COMPLICATIONS, SOCIAL SUPPORT

WHEN MEDICATION IS NEEDED 2

A COMPREHENSIVE HISTORY, EXAM, AND RISK BENEFIT ASSESSMENT NEEDS TO BE DONE ON A CASE BY CASE BASIS IN PARTNERSHIP WITH THE PATIENT AND WHENEVER POSSIBLE THEIR PARTNER, TO PROVIDE A CLINICAL RECOMMENDATION AND INFORMED CONSENT

THE ANALYSIS MUST ALWAYS INCLUDE THE DATA IN THE PATIENT VS. THE DATA IN THE LITERATURE.

DATA IN THE PATIENT CAN OFTEN TRUMP DATA IN THE LITERATURE THERE IS NO “BEST” MEDICATION IN PREGNANCY

IS THE MEDICATION SAFE? DEPENDS ON WHERE WE THINK IT WORKS: THE BRAIN VS. THE STOMACH

•  FIRST ? .... WHAT IS THE ONE OF THE MOST COMMONLY TREATED DISORDERS IN THE FIRST TRIMESTER:

•  ANSWER….NAUSEA AND VOMITING (N/V)

•  SECOND ? GUT REACTION (NO PUN INTENEDED) : •  WHAT’S A SAFER MEDICATION TO USE IN PREGANCY A

MEDICTAION TO TREAT SCHIZOPHRENIA OR A MEDICATION TO TREAT N/V?

WHEN MEDICATION IS NEEDED 4: IS IT SAFE? DEPENDS ON WHERE WE THINK THE MEDICATION

WORKS: THE BRAIN VS. THE STOMACH •  THIRD ?.....WHERE DO MEDICATIONS THAT TREAT N/V WORK…..THE

STOMACH??? •  ANSWER: THE BRAIN

•  FOURTH ? HOW DO THEY WORK IN THE BRAIN??? •  ANSWER: ON THE SAME NEUROTRANSMITTER SYSTEMS THAT ARE USED

TO TREAT DEPRESSION, ANXIETY, AND PSYCHOTIC DISORDERS

•  ANSWER TO QUESTION 2: •  THE VERY SAME MEDICINE THAT TREATS NAUSEA TREATS

SCHIZOPHRENIA….BIAS MATTERS….

TREATING PMDS WITH SELECTIVE SEROTONIN REUPTAKE INHIBITORS (SSRIs)

•  SSRIs: USED TO TREAT DEPRESSION, ANXIETTY, OCD

•  FLUOXETINE/PROZAC •  SERTRALINE/ZOLOFT •  CITALOPRAM/CELEXA •  S-‐CITALOPRAM/LEXAPRO •  PAROXETINE/PAXIL •  FLUVOXAMINE/LUVOX

TREATING PMDS WITH SSRI’S IN PREGNANCY: THE MESS

•  MULTIPLE CONTRADICTORY STUDIES SUGGESTING OR REFUTING –  TERATOGENIC EFFECTS ON MULTIPLE ORGAN SYSTEMS/ADVERSE

FETAL EFFECTS –  PERSISTENT PULMONARY HYPERTENSION –  POOR NEONATAL ADAPTATION –  DEVELOPMENTAL DISORDERS


•  MULTIPLE CONFOUNDERS •  IS MATERNAL DEPRESSION CONTROLLED FOR , •  STUDY DESIGN (RETROSPECTIVE, PRESCRIPTION LOGS (DID

MOM ACTUALLY TAKE THE MEDICATIONS, DATA BASE REVIEW, ARE CLINICALLY SIGNFICANT ABNORMALITIES SEPARATED FROM THOSE THAT RESOLVE SPONTANEOUSLY


•  SORTING THROUGH THE DATA TAKES CONTINUED VIGILANCE •  STUDIES OFTEN HAVE MULTIPLE CONFOUNDERS •  IS MATERNAL DEPRESSION CONTROLLED FOR ? •  STUDY DESIGN (RETROSPECTIVE, PRESCRIPTION LOGS (DID

MOM ACTUALLY TAKE THE MEDICATIONS, DATA BASE REVIEW, ARE CLINICALLY SIGNFICANT ABNORMALITIES SEPARATED FROM THOSE THAT RESOLVE SPONTANEOUSLY

•  NEW STUDIES COME OUT VERY FREQUENTLY, INFORMATION NEEDS TO BE INTEGRATED

NOT SEPARATED. ONE STUDY DOES NOT THE STORY MAKE.

SSRI’S IN PREGNANCY: WHY THE CONCERN/TERATOGENICITY

•  NATURE’S WAY 3% BASELINE RISK OF CM’S, CV DEFECTS MOST COMMON AT 1%

•  WHAT IS A MAJOR TERTAOGEN? •  EXPOSURE TO A MAJOR TERATOGEN DURING GESTATION

RESULTS IN PREDICTABLE PATTERNS OF MALFORMATIONS ASSOCIATED WITH A CRITICAL PERIOD OF ORGANOGENESIS AND HAS A BIOLOGICALY PLAUSIBLE MECHANISM TO EXPLAIN THE TERATOGENICITY.

•  EX: VALPROIC ACID, FOLATE CONSUMPTION AND NTD’S

SSRI’S IN PREGNANCY: WHY THE CONCERN/TERATOGENICITY

WHEN CONSIDERING THE

LITERATURE AS A WHOLE: SSRI’S AS A CLASS DO NOT MEET THE CRITERIA TO BE DEFINED AS A MAJOR TERATOGEN…MORE ON

PAXIL TO COME

SSRI’S IN PREGNANCY: WHAT’S THE RISK

THOUGH SSRI’S AS A CLASS DO NOT APPEAR TO BE MAJOR TERATOGENS, THAT DOES NOT MEAN THEY ARE WITHOUT RISK. THERE IS STILL DEBATE ABOUT: CARDIOVASCULAR DEFECTS (SEPTAL WALL) RARE ANATOMIC DEFECTS IN STOMACH WALL AND SKULL

FORMATION, ANENCEPHALY PPHN PNA SGA INCREASED RISK OF PRETERM BIRTH

SSRI’S IN PREGNANCY: TERATOGENICITY

•  GESTATIONAL EXPOSURE TO SSRIS HAVE BEEN ASSOCIATED (IN SOME STUDIES) WITH RARE DEFECTS IN GASTROINTESTINAL (OMPHALOCELE INCIDENCE 1:2,000), BONE FORMATION (CRANIOSYNOSTOSIS INCIDENCE 1 :5,000) AND NEUROLOGIC DEFECTS ANENCEPHALY (1:10,000)

•  THE LITERATURE IS CONTRADICTORY AND OTHER STUDIES FIND NO ASSOCIATIONS

•  IF IT IS TRUE THEN THE MOST COMMON ABNORMALITY OMPHALOCELE (SPONTANEOUS RESOLVED VS SURGICAL REPIAR) WOULD HAVE AN INCREASED RISK OF 1:1000 OR 96.999% OF HAVING A BABY WITHOUT CM’S

•  HELP ME UNDERSTAND THE BIOLOGIC MECHANISM LINKING THE THREE?

SSRI’S IN PREGNANCY: CARDIOVASCULAR MALFORMATIONS (CVM’S)

•  CVM’S MOST COMMON CM; 1%, MOST COMMON ASD/VSD •  OFTEN ASYMTPOMATIC/RESOLVE SPONTANEOUSLY •  PAXIL: INITIAL DATA INDICATES PAXIL INC RISK OF CVM TO

2%. •  HOWEVER….THE LARGEST PROSPECTIVE AND DATABASE

STUDY FOUND NO ASSOCIATION BETWEEN PAXIL AND CVM’S RATE .7% EXPOSED/UNEXPOSED . AM J PSYCHIATRY

•  INITIAL STUDIES DID NOT TAKE INTO ACCOUNT CLINICAL SIGNFIANCE OF LESIONS….ASYMTPOMATIC AND SYMTPOMATIC WERE COMBINED

•  PEDERSON ET AL. 2009 DATA BASE STUDY: SERTRALINE, FLUOXETINE, CITALOPRAM WERE ASSOCIATED WITH SEPTAL DEFECTS, WHILE PAXIL CAME OUT CLEAN? HOW DO YOU INTERPRET THIS?

SSRI’S IN PREGNANCY: PERSISTENT PULMONARY HYPERTENSION

(PPHN) FAILURE OF PULMONARY VASCULATURE TO VASODIALTE

•  INCIDENCE-‐ 1:1000 LIVE BIRTHS •  PRESENTS WITH HYPOXEMIA, RESPIRATORY DISTRESS,

REQUIRES NICU ADMISSION,INTUBATION,ECMO •  MORTALITY: 15%

SSRI’S IN PREGNANCY: PPHN CHAMBERS ET AL, 2008. EXPOSURE TO FLUOXETINE AFTER WEEK

20 IN PREGNANCY RESULTS IN A SIX FOLD INCREASE IN RR OF PPHN..FDA BLACK BOX….NOW REMOVED WHY???

SINCE THEN: NO STUDY HAS BEEN CONDUCTED THAT HAS ASSOCIATED SSRIS WITH A SIX FOLD INCREASE IN PPHN

STUDIES HAVE RANGED FROM NO ASSOCIATION OF SSRI EXPOSURE TO PPHN TO RISKS OF 2-‐4%

AT UCLA WE HAVE NEVER SEEN A CASE OF PPHN IN THE LITERATURE NO BABIES HAVE EVER DIED FROM

EXPOSURE TO SSRIS IN THE PPHN GROUP WHILE FATALITIES ARE ASSOCIATED WITH THE SPONTANEOUS FORM OF PPHN

BIOLOGIC MECHANISM: 5-‐HT EFFECTS ON SMOOOTH MUSCLE

SSRI’S IN PREGNANCY: PERVASIVE DEVELOPMENTAL/AUTISTIC

SPECTRUM DISORDERS (PDD’S) SEVERAL RECENT RETROSPECTIVE STUDIES LOOKING AT INCIDENCE OF PDD’S

SOME STUDIES FIND MINOR ASSOCIATION, SOME FIND NONE SEVERE METHODOLOGIC FLAWS IN CERTAIN STUDIES, MULTIPLE

CONFOUNDS INCLUDING DEPRESSION BOTTOM LINE: THERE IS NO CONVINCING EVEIDENCE THAT SSRI’S/

ANTIDEPRESSANTS INCREASE THE RISK OR CAUSE AUTISTIC SPECTRUM DISORDERS AND IF IT WERE TO BE BORN OUT IN FUTURE STUDIES IT WOULD LIKLEY ACCOUNT FOR A FRACTION OF CASES,

SSRI’S IN BREAST FEEDING ALL MEDICATIONS PASS INTO THE BREASTMILK-‐THERE IS NO

NON EXPOSURE, THERE IS NO “BEST” SSRI IN BREASTFEEDING SERTRALINE AND PAROXETINE GET EXCRETED INTO BREAST MILK IN LOWER CONCENTRATIONS THEN FLUOXETINE, CITALOPRAM, S-‐CITALOPRAM, AND FLUVOXAMINE EXPOSURE IN PREGNANCY IS ALWAYS GREATER THAN EXPOSURE DURING BREASTFEEDING POTENTIAL RISKS INCLUDE SEDATION, FEEDING DIFFICULTIES,

MOOD STABILIZERS IN PMDS

USED TO TREAT BIPOLAR DISORDER, REFRACTORY DEPRESSION -‐ DIVALPROIC ACID/DEPAKOTE -‐ LAMOTRIGINE/LAMICTAL -‐ LITHIUM -‐ TOPIRAMATE/TOPOMAX -‐ CARBAMAZEPINE/TEGRETOL

MOOD STABILIZERS IN PMDS TERATOGENICITY

-‐ DIVALPROIC ACID: 4% RISK OF NEURAL TUBE DEFICITS, DECREASED IQ IN EXPOSED INFANTS -‐ LAMOTRIGINE ? CLEFT PALATE -‐ LITHIUM: EBSTEINS ANAMOLY (CARDIAC) INCIDENCE 1:10000 GENERAL POPULATION, 1:2000 LITHIUM EXPOSED -‐ TOPIRAMATE: HYPOSPADIAS -‐ CARBAMAZEPINE: NT DEFECTS

MOOD STABILIZERS IN BREAST FEEDING

LACK OF SLEEP INCREASES RISK OF RELAPSE IN MOOD DISORDERS ALL MEDICTAIONS PASS INTO BREASTMILK LITHIUM IS CONTRAINDICATED IN BF OTHER MEDS MAY BE USED ALWAYS A RISK BENEFIT ANALYSIS

ATYPICAL ANTIPSYCHOTICS IN PMDS USED TO TREAT PSYCHOSIS, MANIA, BIPOLAR DEPRESSION,

SEVERE DEPRESSION, ANXIETY/OCD, REFRACTORY INSOMNIA OLANZAPINE/ZYPREXA QUETIAPINE/SEROQUEL RISPERIDONE/RISPERDAL ZIPRASIDONE/GEODON ARIPIPRAZOLE/ABILIFY

AS A CLASS DO NOT APPEAR TO BE MAJOR TERATOGENS MORE DATA FOR OLANZAPINE AND QUETIAPINE, LIMITED DATA ON ARIPIPRAZOLE/ZIPRASIDONE, BF IS AGAIN A RISK BENEFIT ANALYSIS

PMD’S WHAT CAN I DO?

•  INCREASE KNOWLEDGE BASE OF PERINATAL MENTAL HEALTH AND TREATMENT

•  DISCUSS RISK FACTORS THAT CONTRIBUTE TO PMD’S. •  HELP NORMALIZE FEELINGS AND EDUCATE PATIENTS ABOUT

PERINATAL MOOD ISSUES AND POSSIBLE TREATMENT OPTIONS.

•  ADDRESS PSYCHOSOCIAL ISSUES INCREASES TRUST AND PATIENT SATISFACTION.

•  GET A CONSULTATION/FORM A PARTNERSHIP WITH A THERAPIST OR MD THAT WITH EXPERTISE IN THIS AREA

REFERENCES •  INFANTACIDE:PSYCHOSOCIAL AND LEGAL PERSPECTIVES ON MOTHERS THAT KILL, EDITED BY

MEG SPINELLI, WASHINTON DC, AMERICAN PSYCHIATRIC PUBLISHING; 2003. •  JONES, I., CRADDOCK, N. SEARCHING FOR THE PUERPERAL TRIGGER: MOLECULAR GENETIC

STUDIES OF BIPOLAR AFFECTIVE PUERPERAL PSYCHOSIS. PSYCHOPHARM BULLETIN, 2007 •  KIM J-‐H ET. AL., A CLOSER LOOK AT DEPRESSION IN MOTHER’S WHO KILL THEIR CHILDREN; IS

IT UNIPOLAR OR BIPOLAR DEPRESSION? J CLIN PSYCH 69:1625-‐31, 2008 •  MARCUS, S.M. DEPRESSION DURING PREGNANCY: RATES, RISKS, AND CONSEQUENCES. CAN J

CLIN PHARMACOL 16:E15-‐E22, 2009 •  OVERPECK ET. AL., RISK FACTORS FOR INFANT HOMICIDE IN THE UNITED STATES. N ENGL J

MED 339:1211-‐1216, 1998 •  OVERPECK ET. AL., NATIONAL UNDERASCERTAINMENT OF SUDDEN UNEXPECTED DEATHS

ASSOCIATED WITH DEATHS OF UNKNOW CAUSE. PEDIATRICS 109;274-‐283, 2002 •  PARRY BL. POSTPARTUM PSYCHIATRIC SYNDROMES, IN COMPREHENSIVE TEXTBOOK OF

PSYCHIATRY 6TH ED, VOL 1 EDITED BY KAPLAN AND SADDOCK. PHIALDELPHIA, WILLIAM AND WILKINS 1995.

•  UGUZ, FARUK ET. AL. POSTPARTUM-‐ONSET OBSESSIVE COMPULSIVE DISORDER: INCIDENCE, CLINICAL FEATURES, AND RELATED FACTORS

•  WISNER KL ET.AL., SYMPTOMATOLOGY OF AFFECTIVE AND PSYCHOTIC ILLNESS RELATED TO CHILD BEARING. J AFFECT DISORD 1994; 30:77-‐87

MERRILL!SPARAGO,!MD! · when!a!patient!has!a! perinatal!mood!disorder (pmd)! •...

Documents

Transcript of MERRILL!SPARAGO,!MD! · when!a!patient!has!a! perinatal!mood!disorder (pmd)! •...