Premenstrual Dysphoric Disorder (PMDD) - Carlie Benson, MD, PGY4 Department of Psychiatry University of Utah Health - University of Utah ...

Premenstrual Dysphoric
   Disorder (PMDD)
     Carlie Benson, MD, PGY4
     Department of Psychiatry
     University of Utah Health

PMDD Diagnostic Criteria
A) 5+ of the following symptoms (need at least 1 from each criterion B & C)
present in the final week before onset of menses (luteal phase), start to
improve within days of menses onset, and become minimal or absent in the
week post-menses (follicular phase) during most menstrual cycles over the
past year:

                                               C) Behavioral/Somatic
      B) Affective Symptoms                         Sypmtoms
   1. Affective lability                   1. Decreased interest
   2. Irritability/Anger                   2. Poor concentration
   3. Depressed mood                       3. Low energy
   4. Anxiety                              4. Change in appetite
                                           5. Change in sleep
                                           6. Feeling overwhelmed
                                           7. Physical Symptoms*

Affective Symptoms
                 Need 1+ symptoms from this list

1. Affective lability – mood swings, feeling suddenly
   sad, increased sensitivity to rejection.
2. Irritability* or Anger – increased interpersonal
   conflicts
3. Depressed mood – feeling hopeless, self-
   depreciating thoughts
4. Anxiety – tension, feeling keyed-up, restlessness

Behavioral and Somatic
                Symptoms
                      Need 1+ symptoms from this list

1.   Decreased interest – work, school, hobbies, relationships
2.   Difficulty in concentration – subjective report
3.   Low energy* – lethargy, fatigability
4.   Change in appetite – overeating, poor appetite, specific food
     cravings
5.   Change in sleep – insomnia or excessive sleep
6.   Overwhelmed – feeling out of control
7.   Physical symptoms – breast swelling/tenderness, joint/muscle
     pain, bloating*, weight gain, dizziness, hot flashes, headaches.

PMDD Dx Criteria Cont.
D) The symptoms cause clinically significant distress or functional
impairment
E) Symptoms are not due to an exacerbation of another disorder
(MDD, panic disorder, dysthymia, personality disorder), though can
co-occur with other disorders
F) Criterion A should be confirmed by prospective ratings during 2+
cycles *prior to confirmation, can be made as a provisional dx
G) Symptoms are not attributable to a substance or medical condition

Menstrual History is Key
• Detailed menstrual history to confirm
  relationship of timing of symptoms with cycle

• Ask about endogenous hormone use
  (infertility treatment, HRT, OCPs)

• Prospective documentation is required

PMS vs PMDD

• PMDD > PMS

• PMS
  –

Disease Course
• May begin anytime after menarche and typically continues
  throughout the reproductive life
• Symptoms may worsen in the pre-menopausal period, but
  then resolve after menopause
• Peak severity of symptoms is typically at onset of menses,
  resolve during follicular phase
• The luteal phase is marked by increased risk for suicide
• Leads to a high economic burden

Epidemiology
• Clinically significant PMS occurs in 3-8% of
  women
• PMDD occurs in 2% of women
• Similar rates cross-culturally
• May be slightly more prevalent in white
  women compared to black women

Risk Factors
• Environmental
    – Stress
    – History of trauma
    – Smoking
    – Seasonal changes
    – Cultural influences
• Genetic
    – Exact heritability is unknown
    – Premenstrual symptoms have variable heritability, ranging from 30% - 80%
• Oral contraceptives may be protective
    – Some hormonal treatments may exacerbate PMDD symptoms
• Comorbidity – history of depressive episodes
    – Many other mental or medical diagnosis may have premenstrual
      exacerbation of symptoms

Copyrights apply

Pathogenesis
• Triggered by changes in female gonadal steroids
  (sex hormones) during the luteal phase
  – Gonadal steroids are a active in the CNS and interact
    with neurotransmitters
  – Other peripheral mechanisms

• Due to an underlying sensitivity to changes in
  gonadal steroids, not due to the gonadal steroids
  themselves

Special Populations

• Menstrual irregularities

• Women without menstruation
  – Hysterectomy

  – Levonorgestrel IUD (Skyla, Mirena, Kyleena,
    Liletta)

Prospective Symptom Trackers
• Daily Record of Severity of Problems (DRSP)
• Prospective Record of the Impact of Severity
  of Menstrual symptoms (PRISM)
• Premenstrual Symptoms Screening Tool
  (PSST)
• Calendar of Premenstrual Experiences (COPE)

Tracking Apps

• Me v PMDD             • T2 Mood Tracker

• Period Tracker        • Mood Log

• CLUE Ovulation        • iMood Journal
  Tracker               • Plus many more…
• Period Tracker Lite

Laboratory Testing

• None required

• Consider TSH

• Consider additional workup for menstrual
 irregularities (hCG, prolactin, FSH)

Differential Diagnosis
• PMS                         • Dysthymia

• Endogenous hormone use      • Menopausal transition

• Dysmenorrhea                • Thyroid disorders

• Major Depressive Disorder   • Substance use disorders

• Bipolar Disorder

Copyrights apply

Serotonergic Treatments
• SSRIs – recommended as first line treatment (non-bipolar
  patients)
   – sertraline*, citalopram, escitalopram, fluoxetine*
   – Similar efficacy as that seen for Tx of MDD
   – Benefit can be expected in first cycle
   – May treat mood sx > somatic sx
   – May respond to lower doses, often doses similr MDD
   – No response with 1st SSRI  try 2nd SSRI  consider trial of 3rd
• SNRIs – paroxetine and venlafaxine (don’t use these)
• Clomipramine (wouldn’t recommend)
                                 * = FDA Approval for PMDD

SSRI Dosing Strategies
• Continuous Therapy
  – Better for more severe sx, incomplete resolution of
    symptoms between cycles, or irregular cycles
• Luteal Phase Therapy
  – Starts on day 14 of the cycle and ends at onset of menses
    or a few days after
• Symptom Onset Therapy
  – Better for women with shorter duration and less severe
    symptoms

NO ---->

Copyrights apply

Oral Contraceptives
• Goal is to suppress the hypothalamic-pituitary-ovarian axis
  and ovulation
• Drospirenone (DRSP) containing combined oral
  contraceptives (COC) are FDA approved for PMDD
   – Start with 3mg DRSP/20mcg EE (4 day pill free interval)  3mg
     DRSP/30mcg EE if sx persist/breakthrough bleeding after 3
     cycles
   – Drospirenone has increased risk of VTE
   – If sx persist consider continuous COC vs adding SSRI
      • 90mcg levonorgestrel/20mcg EE
      • Continuous COCs have higher rates of continuous vaginal bleeding

GnRH Agonists                       rd
                                    – 3 Line Tx
• Only to be tried after trial of SSRI and COCs
• Leuprolide 3.75mg monthly injection
   – Given with progestin-estrogen add back
   – 1mg oral estradiol + 100mg micronized progesterone
      • Can use other equivalent forms of hormones (transdermal)

• Long-term safety of GnRH agonists and
  hormonal replacement therapy is unknown

Supplements
• Possibly helpful
  – Vitex agnus castus (chasteberry) 20-40mg daily

• Maybe helpful, not risk free
  – Calcium 600mg BID
  – Vitamin B6 – up to 100mg daily

• No data to support
  – primrose oil, vitamin E, and Mg

Complimentary Treatments
• Cognitive Behavioral Therapy
   – Adjunctively with SSRI
• Exercise
• Stress reduction
• Mindfulness
• Diet
• Sleep hygiene

Take Home Points
• Diagnosis must be confirmed with 2 month
  prospective symptom tracking
• Need symptom free follicular phase for diagnosis
• SSRIs are first line treatment, good efficacy
• COCs are reasonable first line alternatives to SSRIs
• Don’t use alprazolam or paroxetine
• Consider non-pharmacologic treatments for mild sx

References
•   American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. Arlington, VA, American Psychiatric
    Association, 2013.
•   https://iapmd.org – Information on apps for PMDD symptom tracking
•   Pearlstein T et Steiner M. ”Premenstrual dysphoric disorder: burden of illness and treatment update.” J Psychiatry Neurosci 2008;33(4):291-301.
•   Schmidt PJ, Nieman LK, Danaceau MA, Adams LF, Rubinow DR. Differential behavioral effects of gonadal steroids in women with and in those
    without premenstrual syndrome. N Engl J Med. 1998;338(4):209-216. doi:10.1056/NEJM199801223380401
•
•   Uptodate.com. 2020. Uptodate. [online] Available at: 
    [Accessed 21 October 2020].
•   Uptodate.com. 2020. Uptodate. [online] Available at: 
    [Accessed 21 October 2020].
•   Uptodate.com. 2020. Uptodate. [online] Available at: 
    [Accessed 21 October 2020].