Choosing antipsychotic by 6t0SpFkz

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									                     By:
Dr. Hani Hamed Dessoki, M.D. Psychiatry
         Associate Prof. Psychiatry
    Acting   Head, Psychiatry Department
              Beni Suef University




                     2010
                    Introduction

 A substantial number of women of childbearing age are
  prescribed psychotropic drugs, and because nearly 50% of
  pregnancies are unplanned, many women are still taking
  them upon becoming pregnant.

 Psychotropic drugs are commonly used to treat psychiatric
  disorders     --    antidepressants,   benzodiazepines,
  antipsychotics, antiepileptics, and lithium.
  FDA: “Use in Pregnancy”-
      Drug categories

 Category A: Controlled studies show no risk
 Category B: No evidence of risk in humans
 Category C: Risk to humans cannot be ruled out
 Category D: positive evidence of risk but it is
  possible in some situations the benefits may
  outweigh the risks {benifit > risk}
 Category X: Toxic, Contraindicated in pregnancy.
  Risks outweigh the benefits in almost every
  situation {risk > benifit}
  Risk Periods for Foetal
 Structural Malformations

2-4 weeks neural tube closure
4-9 weeks heart is forming
6-9 weeks is when the oral cleft closes
by 12 weeks organogenesis is completed
                    Teratogen

 Word derived from "terato" meaning monster and "gen,"
  to give rise to, so teratogens give rise to monsters (not
  really).

 Non-genetic factors that interfere with normal
  embryonic and fetal differentiation and morphogenesis.

 Children who have been exposed to teratogens in utero
  will not pass their defect on to their children.
        Important factors in
          Teratogenicity
 Time. The gestational age of the fetus at the time of the
  exposure to the teratogen. Different organs of the body are
  forming at different times. There is an "all or none" period
  in the first two weeks where the fetus is generally not
  susceptible to teratogens.
 Dosage. To how much of the teratogen was the fetus
  exposed.
 The genotype of the fetus. The fetus may be more or less
  resistant to the teratogen because of inactivation of the
  teratogen.
 The genotype of the mother. Mothers also differ in their
  ability to detoxify the teratogen.
    Two Basic Assumptions

 1. All medications cross the placenta and also enter
 breast milk.
 2. We do not yet know all the potential risks from
 medication exposure.

 We talk about the “Risk/Benefit ratio”.
 Risks of treatment vs the benefits of treatment or
 risks of treatment vs risks of non-treatment.
Psychotropics in Pregnancy: General
          Considerations
 Don’t: Consider non-pharmacological measures
 Normal incidence: 2-4% major, 15% minor
 Discuss & document Pros/Cons: balance risks and
 benefits & provide written information
 Obtain & document informed consent
 Post-prescription follow up
 Delivery: should the dose be changed around
 delivery time
Psychotropics in Pregnancy: General
        Considerations cont’d
 Explain risks and benefits of medication and non-
 medication treatment approaches, respect the
 mother’s wishes, document decision-making.
 Don’t use medication unless truly necessary,
 especially during the first trimester.
 Dose medications to adequately treat disorders
 (i.e., don’t under-medicate to decrease drug
  exposure).
Maternal Psychiatric Illness, What
    are the risks Prenatally?

 Effects on Mother and foetus and/or baby.
 Poor compliance with obstetric/medical
 care
 Poor maternal health/nutrition
 Abuse of alcohol and cigarettes
 Abuse of other substances including over
 the counter remedies
 Suicidality, self-harm, recklessness
Maternal Psychiatric Illness, What
   are the risks - Postnatally?

 Deficits in mother-infant attachment
 Neurobehavioural sequelae
 Increased failure to breastfeed
 Separations at home, possible psychiatric
 hospitalisation
 Abuse, neglect, self harm, recklessness
 Rarely, suicidality / infanticide
Maternal Psychiatric Illness,
       Further risks

 Effects on Family and Environment
 Reduced care of other children
 Emotional neglect of other children
 Marital disturbance
 Occupational deterioration
 Reduced social network
Potential effects of exposure to illness and
     medications for the foetus/baby


 Miscarriage
 Structural Malformations/Teratogenicity
 Intra-uterine death
 Growth Impairment (low birth wt.)
 Prematurity
 Neonatal toxicity and withdrawal
 Behavioural teratogenicity
   cognitive, emotional, social, behavioural
                DRUGS OR SUBSTANCES
               SUSPECTED OR PROVEN
              TO BE HUMAN TERATOGENS

   ACE inhibitors                Etretinate
   Alcohol                       Isotretinoin
   Aminopterin                   Lithium
   Androgens                     Methimazole
   Busulfan                      Methotrexate
   Carbamazepine                 Penicillamine
   Chlorbiphenyls                Phenytoin
   Coumadins                     Radioactive iodine
   Cyclophosphamide              Tetracycline
   Danazol                       Trimethadione
            Diethylstilbestrol (DES)       Valproic-acid

Annie Ouellet, FRCS,Maternal-Fetal Medicine.University of Ottawa
 Measuring the Risk of Psychiatric
   Medicines During Pregnancy


When testing a psychiatric medication's effects on
 pregnancy, doctor's look for three things:
 Occurrence      of birth defects (structural
 teratogenesis)
 Occurrence of behavioral problems (behavioral
 teratogenesis)
 Occurrence of unusual symptoms directly after
 birth (perinatal syndromes)
      Antipsychotic Meds-
          Neuroleptics
 First-generation:        Atypical Antipsychotics
  Phenothiazines=               (2nd and 3rd gen)=
     Thorazine,                   Clozaril,
                                  Zyprexa,
     Mellaril,                    Risperdal,
     Stelazine,                   Seroquel,
                                  Zeldox
Non     Phenothiazines=          Serdolect
                                  Invega,
      Haldol
                                  Abilify
  (butyrophenones)
  (high potency)
                   Neuroleptics


Cat B: Clozapine (clozapex)
Cat C:
•Trifluoperazine, Thioridazine(mellaril), Droperidol ,
Pimozide, Fluphenazine (modecate),
•Flupenthixol, Zuclopenthixol (Some cases of birth defects
and gestational metabolic complications were recorded).
               Haloperidol

 Haloperidol is rated FDA Pregnancy Category C.


 It has been on the market for more than 40
  years, and there is no evidence that, when used
  during pregnancy, they increase the rates of major
  malformations.
 It is associated with no increased risk to fetus or
  baby, and are recommended for use during
  pregnancy in high-risk patients.
   Chlorpromazine (Thorazine)
 Chlorpromazine is rated FDA Pregnancy Category C.
  In animals, increased risk of congenital malformations
  (involving skeletal and central nervous systems, eye,
  cleft palate, fetal death, and reduced fetal weight gain).

 NEONATAL SIDE EFFECTS: There are reported
  instances of prolonged jaundice, extrapyramidal signs,
  hyperreflexia or hyporeflexia in newborn infants whose
  mothers received phenothiazines prenatally.
            Risperidone

Risperidone is rated FDA Pregnancy
 Category C.
Some studies concluded that an increased
 risk of spontaneous abortions and fetal
 teratogenicity could not be identified in
 pregnant     women administered      with
 risperidone.
             Risperdal Consta

 Risperdal Consta is rated FDA Pregnancy Category C.
 There are no adequate data from the use of
 risperidone in pregnant women.
 According     to    postmarketing     data     reversible
 extrapyramidal symptoms in the neonate were observed
 following the use of risperidone during the last trimester
 of pregnancy.
 The potential risk for humans is unknown. Therefore,
 RISPERDAL CONSTA should not be used during
 pregnancy unless clearly necessary.
              Olanzapine

Olanzapine    is rated FDA Pregnancy
 Category C.
 23     olanzapine-exposed    pregnancies
 resulted in no increase in major or minor
 anomalies.
             Aripiprazole

 Aripiprazole is rated FDA Pregnancy Category
  C.
 The benefits from use in pregnant women may be
  acceptable despite the risk.
                Quetiapine

 Quetiapine is rated FDA Pregnancy Category C.
 In human studies, quetiapine showed the lowest
  amount of placental passage (mean = 23.8%, SD =
  11.0) when compared with both FGAs (haloperidol)
  and SGAs (risperidone and olanzapine).
 Possibility of low birth weights and higher rates of
  spontaneous abortions (not statistically significant
  due to low sample size).
               Ziprasidone

 Ziprasidone is rated FDA Pregnancy Category C.
 In animal studies, ziprasidone demonstrated
  developmental toxicity, including possible
  teratogenic effects (mainly represented by
  ventricular    septum defects     and   kidney
  malformations), at doses similar to the human
  therapeutic dose.
 At present, no human data are available.
                Sertindole

 Sertindole is rated FDA Pregnancy Category C.
 Though no human data are available on this drug
  that, however, has not demonstrated any
  teratogenic effects in animal reproduction studies.
       Evidence Based Study
 Reviewed information was too limited to draw
  definite conclusions on structural teratogenicity of
  FGAs and SGAs.
 Both classes of drugs seem to be associated with an
  increased risk of neonatal complications.
 However, most SGAs appear to increase risk of
  gestational metabolic complications and babies large
  for gestational age and with mean birth weight
  significantly heavier as compared with those exposed
  to FGAs.
                            Gentile S., Schizophrenia Bulletin (2008)
 Evidence Based Study                                 cont,d


 These risks have been reported rarely with FGAs.
 Hence, the choice of the less harmful option in
  pregnancy should be limited to FGAs in drug-
  naive patients.
 When pregnancy occurs during antipsychotic
  treatment, the choice to continue the previous
  therapy should be preferred.


                          Gentile S., Schizophrenia Bulletin (2008)
     EPS Treatments during
           Pregnancy

 Diphenhydramine is probably safest although birth
  defects rate somewhat higher with 1st trimester
  exposure; increased malformation rate with
  benztropine, trihexyphenidyl, and especially
  amantadine.
 Propranolol is reasonably safe.
Psychotropics and Breastfeeding

              It is widely accepted that
              there are many benefits in
              breastfeeding           both
              biologically and in terms of
              mother-baby attachment.

              Do these benefits outweigh
              the   potential   risks  of
               psychotropic ingestion?
 Adverse Effects of Psychotropics
        on Breastfeeding

Antipsychotics
  Generally OK to breastfeed
  Some adverse effects noted.
   Typical antipsychotics
 As Haloperidol (Haldol); especially at high dose,
  have occasionally been associated with adverse
  reactions in breastfed infants (eg urinary retention,
  dystonic reactions).

 Chlorpromazine as a drug "for which the effect on
  nursing infants is unknown but may be of
  concern".
     Atypical antipsychotics
 Preliminary data suggest that olanzapine (Zyprexa) and
  risperidone (Risperdal) have low infant doses relative to the
  maternal weight-adjusted dose and, given the lower adverse
  effects in the mother, these medications are being increasingly
  used during lactation (safest).

 Prolactin-sparing antipsychotic may be useful, e.g., quetiapine.

 Clozapine (Clozaril) contraindicated in breastfeeding (due to
  high concentrations in breast milk) unless strongly indicated
  for maternal well-being.
        Take-home Messages

 Evidence-based information from epidemiologic
  studies indicates that most psychotropic drugs are
  relatively safe for use during pregnancy.

 No long-term neuropsychological effects have been
  seen in children exposed as a fetus.
         Take-home Messages

 Infants who have been exposed to neuroleptics
  throughout pregnancy should be watched carefully
  after birth for any signs of extrapyramidal symptoms.

 A woman requiring antipsychotic medication during
  pregnancy should not change her treatment if she is
  well controlled, as it is important for her child that she
  be a well-functioning individual who can adequately
  interact with and take care of her baby.
Please, give only good fertilizer…

								
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