Prescribing in pregnancy; Depression - James Begley RPN,RNP,RNT - HSE

Prescribing in pregnancy;
       Depression

        James Begley RPN,RNP,RNT

Case presentation
 Sarah is 32 years old.
 Married to Sean ten months.
 Pregnant with first child.
 20/40 weeks gestation.
 Works as recruitment manager.

Presenting Complaint
 Sarah was referred by Midwife in Maternity
  OPD who was concerned.
 Sarah was ‘not coping well’ with
  pregnancy.
 Midwife reported Sarah was making
  strange comments about being pregnant,
  was tearful and distressed.

Initial review
   Reviewed Sarah in Maternity OPD accompanied
    by her husband Sean.
   Sarah presented as being very emotional, tearful
    and admitted to feeling depressed.
   Admits to recent panic attacks and finding it
    difficult to cope with being pregnant.
   She was not very forthcoming, therefore I asked
    husband to leave in the hope that she might
    open up more.

History of Presenting Complaint
 Sarah informed me she had psychiatric history;
-Treated for Bulimia Nervosa at age of 17 years as
  inpatient, but has not binged or purged herself in
  several years.
-Also diagnosed with generalised anxiety disorder
  and depression previously and has had inpatient
  treatment for these.
-She reported that her husband was unaware of
  her psychiatric history.

Mental state exam
  Mood: Objectively-labile, tearful and anxious.
           Subjectively- depressed, anxious.
Poor concentration.
Little interest, energy, motivation.
Changes in appetite, no binging/purging
Poor sleep,(2-3 hours per night)
 Thought form;
Negative in outlook, hopeless, guilty,
Denies having any psychotic symptoms.
Logical and coherent.

Mental state exam
 Thought content;
Vague suicidal ideations.
No thoughts of self harm.
No death wish
No homicidal ideas but admits wouldn’t be upset if
  had miscarriage.
Preoccupied with body changes/image and
  pregnancy

Social history;
Recruitment manager,
Good circle of friends,
Denies alcohol/substance use.

Mental state exam
 Family History;
Supportive husband.
History of depression in patients maternal aunt.

Insight
Reports if pregnancy was over she would be ok,
 the pregnancy is the problem.

Current medication
   Had attended GP regarding poor sleep.
    Was prescribed Zopiclone 7.5mg nocte,
    but Sarah informed me that she had not
    taken it in case it would effect the baby.

   She was not taking any other medication.

Impression
   32 year old Married lady, 20/40 weeks
    gestation presenting with symptoms of
    depression, anxiety and panic attacks on a
    background history of bulimia nervosa,
    depression and generalised anxiety
    disorder.

Plan
   Advised Sarah to disclose her past history to her
    husband who was supportive.

   Discussed case with consultant psychiatrist with
    special interest in mental health and pregnancy;

-Advised admission to acute unit for assessment
  and possible commencement of antidepressant.

-Psychology input recommended to address
  issues with body image and coping mechanisms

Plan implementation
   Sarah refused admission to hospital but agreed
    to disclose her history to her husband.
   Consultant psychiatrist recommended to start
    Amitriptyline 25mg mane as Sarah was
    agreeable to take medication.
   CMHN to monitor and provide supportive
    counselling.
   Outpatients review in six weeks.

Pregnancy and Medication –
Issues for consideration;

 Physiological changes
 Pharmacokinetics
 Teratology
 Choice of medication

Definition of terms
   Pharmacokinetics
     Studyof the course of drug absorption, distribution,
      metabolism and excretion
   Pharmacodynamics
     Study of the biochemical and physiological effects of
      drugs and their mechanisms of action
   Plasma half-life
     The   time taken for drug concentration to fall by 50%

Definitions
•Bioavailability
   Extent to which a drug is absorbed systemically. It is
   dependent upon tablet formulation, gut motility, disease
   states and first pass effect.

•Volume of distribution
   The theoretical fluid volume which would contain the
   total body content of a drug at a concentration equal to
   the plasma concentration. Drugs that are highly
   lipophilic and extensively tissue bound have a large
   volume of distribution.

Physiological changes in
pregnancy
  in plasma volume
  in cardiac output
  in renal blood flow and Glomoular
  Filtration Rate
 Induction of liver enzyme pathways
  in plasma protein content
 Delayed gastric emptying

Pharmacokinetics

    volume of distribution

    plasma concentration

    excretion (renal excretion)

    hepatic metabolism

Teratogen
   An agent that causes the production of physical
    defects in the developing embryo.

   An agent which when administered to the
    pregnant mother directly or indirectly causes
    structural or functional abnormalities in the fetus,
    or in the child after birth, though these may not
    become apparent until later life.

Teratology- influencing factors
 dose
 exposure time
 Bioavailability (extent absorbed)
 degradation products
 drug interactions

Timing of exposure
   Important determinant of risk
   N.B. to determine no. of weeks post-conception
   3 stages
     Pre-embryonic       period 0-17 days
          “all or nothing effect”
          toxic insult leads to either death of zygote/blastocyst or
           replacement of damaged cells & intact survival

     Embryonic      period (18 days – 8 weeks)
          fetus most vulnerable to toxins affecting organogenesis

Timing of exposure contd.
   Fetal period (week 9 – birth)
     some  systems e.g. CNS & genitals, remain
      vulnerable; functional defects

   Exposure close to term
     neonatal   effects or withdrawal effects

   Delayed effects are also possible causing effects
    years after exposure in utero
     E.g.   diethylstilbestrol- across generations

Early development             Main embryonic period (weeks)                    Fetal period (weeks)

  1        2        3     4       5       6      7     8       9      16     32       38

                              Neural tube defects       Mental retardation                 CNS

                              TA, ASD, and VSD                HEART

                         Amelia/Meromelia             LIMBS

                                   Cleft lip            UPPER LIP

                                 Low-set malformed ears and deafness              EARS

                                 Microphthalmia, cataracts,glaucoma            EYES

                                                     Enamel hypoplasia             TEETH

                                                      Cleft palate           PALATE

                                                           Masculinsation             GENITALIA

 Embryo
 Embryo Death
        Death                    Major
                                 Major congenital
                                       congenital anomalies
                                                  anomalies                  Functional
                                                                             Functional &
                                                                                        & minor
                                                                                          minor anomalies
                                                                                                anomalies
      Common
      Common site(s)
             site(s) of
                     of action
                        action                 Highly
                                               Highly sensitive
                                                      sensitive period
                                                                period                Less
                                                                                      Less sensitive
                                                                                           sensitive period
                                                                                                     period

Teratology-Thalidomide;
a lesson for prescribers

History- Thalidomide
   Marketed in 1957 for nausea and morning
    sickness
   “drug of choice to help pregnant women”
   Known as Contergan but also incorporated into
    many over the counter preparations
   Licensed in Europe and Australia and Japan
   First affected child born in West Germany in
    1956

Abnormal limb development
secondary to thalidomide ingested
by pregnant mother
   Thalidomide is a tranquiliser,
   sedative & immunosuppressant
   Critical exposure window
   24 to 36 days post fertilisation
   Defects :
       amelia - no limbs
       micromelia - short limbs
       cardiac defects
       haemangiomas
       defects of urinary tract
       defects of digestive tract

Foetal Alcohol Syndrome
   thin upper lip
   short palpebral fissures
   flat nasal bridge
   short nose
   elongated philtrum
   microcephaly
   mental retardation
   cardiac abnormalities
   joint abnormalities

Principles of prescribing in
pregnancy
   Only when necessary
   Consider gestational period
   Seek advice- safety data
   Avoid drugs known to be harmful
   Use lowest effective dose for the shortest time
   Avoid polypharmacy if possible
   Use older, more established drugs
   Avoid herbal remedies
   Counsel to improve compliance

Depression & Pregnancy
   Women are at increased risk of
    depression when pregnant

   On average,12%-15% of pregnant women
    have depressive episode

     (Udechuku et al, 2010; Taylor et al 2012)

Depression & Pregnancy
 In a meta-analysis, it was reported that the
  prevalence of depression in pregnancy is
-3.8% at end of 1st trimester,
-4.9% at end of second trimester
-3.1%at the end of the 3rd trimester.

                           (Gavin et al, 2005)

Depression & Pregnancy
 Difficult to diagnose-
Natural hormonal changes- mood variation
Sleep disturbance,
Appetite variations,
Reduced concentration,
Lethargy
Loss of libido
Anxiety about becoming mother.

Treatment choice
   Mild to moderate depression in pregnancy
-   Self help strategies (exercise, family
    support)
-   Non directive counselling delivered in the
    home (listening visits)
-   Brief cognitive therapy and interpersonal
    psychotherapy.
                        (NICE Guidelines, 2007)

When antidepressant is needed?

   Antidepressant drugs should be
    considered for women with mild
    depression during pregnancy or the
    postnatal period if they have a history of
    severe depression and they decline, or
    their symptoms do not respond to,
    psychological treatments. (NICE,2007)

Treatment choice- medication
   When choosing an antidepressant for pregnant
    or breastfeeding women, prescribers should,
    while bearing in mind that the safety of these
    drugs is not well understood, take into account
    that:
      Tricyclic antidepressants, such as Amitriptyline,
      Imipramine and Nortriptyline, have lower known risks
      during pregnancy than other antidepressants
     Most tricyclic antidepressants have a higher fatal
      toxicity index than selective serotonin reuptake
      inhibitors (SSRIs)
     Fluoxetine is the SSRI with the lowest known risk
      during pregnancy

Treatment choice- medication
    Imipramine, Nortriptyline and Sertraline are present in breast milk at
    relatively low levels
    Citalopram and Fluoxetine are present in breast milk at relatively
    high levels
    SSRIs taken after 20 weeks’ gestation may be associated with an
    increased risk of persistent pulmonary hypertension in the neonate
    Paroxetine taken in the first trimester may be associated with foetal
    heart defects
   Venlafaxine may be associated with increased risk of high blood
    pressure at high doses, higher toxicity in overdose than SSRIs and
    some tricyclic antidepressants, and increased difficulty in withdrawal
   all antidepressants carry the risk of withdrawal or toxicity in
    neonates; in most cases the effects are mild and self limiting.
                                                                (NICE,2007)

Choosing the medication
   When prescribing a drug for a woman with a mental
    disorder who is planning a pregnancy, pregnant or
    breastfeeding, prescribers should:
    • choose drugs with lower risk profiles for the mother and the foetus
       or infant
    • start at the lowest effective dose, and slowly increase it; this is
       particularly important where the risks may be dose related
    • use monotherapy in preference to combination treatment
    • consider additional precautions for preterm, low birth weight or
       sick infants.                                      (NICE, 2007)

   Pregnant women with first episode of depression should be
    prescribed an SSRI (other than Peroxetine) as a treatment.
    (Udechuku et al, 2010)

General Risks
1.   Risk to the foetus: It should also be
     noted that the background risk of foetal
     malformations in the general population
     is between 2% and 4%.
2.   Risk of not treating mental disorder: risk
     to mothers physical and mental
     wellbeing, risk to foetus, family.
3.   Risk of treating disorder; side effects,
     foetus malformation (teratrogenesis),
     withdrawal effects, toxicity.

   Depression in pregnancy has been
    associated with obstetric complications,
    still births, suicide attempts, post natal
    depression, infanticide, low birth weights
    (Bonari et al, 2004)

Back to Sarah
   Sarah continued to take amitriptyline and an
    improvement was noted.
   She was sleeping better, had no
    suicidal/homicidal thoughts.
   She was optimistic about her future, and looking
    forward to motherhood.
   Received support from psychology and CMHN.
   Had baby boy, Jack 7lbs 8oz. All well.

References
   Bonari, L., Pinto, N., Ahn, E., et al. (2004) Perinatal risks of untreated
    depression during pregnancy. Canadian Journal of Psychiatry, 49, 726–
    735.
   Gavin, N. I., Gaynes, B. N., Lohr, K. N., et al. (2005) Perinatal
    depression: a systematic review of prevalence and incidence. Obstetrics
    and Gynaecology, 106, 1071–1083.
   Taylor, D., Paton, C., Kapur, S. (2012) The Maudsley prescribing
    guidelines in psychiatry 11th ed. Wiley-Blackwell. UK.

   National Institute of Clinical Excellence (2007) Antenatal and Postnatal
    mental health; clinical management and service Guidance.
    guidance.nice.org.uk/cg45

   Udechuku, A., Nquyen, T., Hill, R., Szego, K. (2010) Antidepressants in
    Pregnancy: a systematic review. Australian New Zealand Journal of
    Psychiatry 44(11) 978-996.