PANCE Blueprint Psychiatry (6%)

Premenstrual dysphoric disorder (PMDD)

Patient will present as → a 26-year-old patient is complaining of depression and anxiety just prior to her menses. The symptoms have been going on for more than 1 year, but are now starting to interfere with her relationships and her productivity at work. One week prior to menses each month she experiences a depressed mood, a feeling of being on edge, increased irritability, difficulty sleeping, a feeling of being overwhelmed, and is easily fatigued. She charted her symptoms daily in a log and returned to the office two cycles later. The log is consistent with the history. Her physical examination and general laboratory profile showed no abnormalities.

During what phase of the menstrual cycle do symptoms of PMDD manifest?
Symptoms occur during the luteal phase of the menstrual cycle and resolve with menstruation.

Key Points:

  • Repeated episodes of significant depression and related symptoms during the week before menstruation

DSM-5 Diagnostic Criteria

In the majority of menstrual cycles, at least five symptoms must be present in the final week before the onset of menses, start to improve within a few days after the onset of menses, and become minimal or absent in the week post menses.

One (or more) of the following symptoms must be present:

  • Marked affective lability (e.g., mood swings; feeling suddenly sad or tearful, or increased sensitivity to rejection).
  • Marked irritability or anger or increased interpersonal conflicts.
  • Marked depressed mood, feelings of hopelessness, or self-deprecating thoughts.
  • Marked anxiety, tension, and/or feelings of being keyed up or on edge.

One (or more) of the following symptoms must additionally be present, to reach a total of five symptoms when combined with symptoms from above.

  • Decreased interest in usual activities (e.g., work, school, friends, hobbies).
  • Subjective difficulty in concentration.
  • Lethargy, easy fatigability, or marked lack of energy.
  • Marked change in appetite; overeating; or specific food cravings.
  • Hypersomnia or insomnia.
  • A sense of being overwhelmed or out of control.
  • Physical symptoms such as breast tenderness or swelling, joint or muscle pain, a sensation of “bloating,” or weight gain.

The symptoms are associated with clinically significant distress or interference with work, school, usual social activities, or relationships with others (e.g., avoidance of social activities; decreased productivity and efficiency at work, school, or home).

SSRIs (fluoxetine 10 mg, sertraline 50 mg qd, etc) are useful for the treatment of PMDD.

  • These medications can be administered continuously during the menstrual cycle or only when the patients experience symptoms.
  • Luteal phase or intermittent administration involves initiating medication at the time of ovulation and stopping it at the beginning of menses.
  • SNRIs such as venlafaxine may also be effective in women with predominantly psychological symptoms.

Other useful agents are benzodiazepines (addictive) and the tricyclic antidepressant clomipramine (25 mg QD as starting dose).

Birth control, low-dose estrogen, and diuretics may also be beneficial.

Gonadotropin-releasing hormone (GnRH) - accelerated bone loss and vasomotor symptoms associated with long-term use of a GnRH agonist will require add-back therapy.

  • Hormonal intervention with monthly intramuscular injections of leuprolide has been reported effective in some patients; however, it should be reserved only for patients unresponsive to first- and second-line agents.

Nutritional supplementation (vitamin B6 up to 100 mg/day, vitamin E up to 600 IU/day, calcium carbonate up to 1200 mg/day, and magnesium up to 500 mg/day) are also commonly used for symptom reduction in some patients with limited results.

Ovariectomy may be considered in severe refractory cases.

Picmonic (Phases of the menstrual cycle and PMDD)

The 28-day menstrual cycle can be described by the ovulatory hormones in two phases: the follicular (proliferative) phase and the luteal (secretory) phase. The follicular phase describes the balance between FSH, estrogen, LH, and ovulation. In PMDD symptoms occur during the luteal phase of the menstrual cycle and resolve with menstruation.

Ovulatory Hormones II – Luteal Phase
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Ovulatory Hormones I – Follicular Phase
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Question 1
 A 26-year-old female presents to her primary care physician with several months of mood swings, which she feels are affecting her work and personal relationships. She states that on roughly a quarter of days each month, she feels highly irritable, sensitive to criticism and rejection, and easily saddened. She also feels that her appetite varies greatly, and on the days when she is particularly emotional, she also feels especially hungry. As a result of these symptoms, her performance at work has suffered, and her boyfriend has been complaining that she is difficult to live with. She is anxious that she cannot “get my mood under control.” The patient has no past medical history, regular periods every 28 days, and no obstetric history. She uses condoms for contraception. Her mother has major depressive disorder, and her father has hypertension and coronary artery disease. At this visit, the patient’s temperature is 98.4°F (36.9°C), pulse is 75/min, blood pressure is 130/76 mmHg, and respirations are 13/min. She appears slightly anxious but has overall normal affect and is pleasantly conversational. Physical exam is unremarkable. Which of the following is the best next step in management?
Reassuring the patient that her feelings are normal is not appropriate in this case, as her mood dysfunction is interfering with her work and personal life. Although some variation in mood is expected and may be physiologic around the time of menstruation, functional impairment should not be dismissed.
Selective serotonin reuptake inhibitor
Combined oral contraceptive therapy
Combined oral contraceptive therapy can be used continuously in PMDD to suppress ovulation and menstruation, thus eliminating the hormonal variations that trigger symptoms. This is considered second-line to SSRIs.
Serotonin-norepinephrine reuptake inhibitor
Serotonin-norepinephrine reuptake inhibitor (SNRI) therapy may sometimes be used for PMDD, but the evidence is not as strong as for SSRIs.
Cognitive behavioral therapy
Referral for cognitive behavioral therapy can be used in conjunction with pharmacologic treatments and is an appropriate step in patients with PMDD that severely affects daily functioning. However, trial of SSRI therapy with reassessment of symptoms is the initial step.
Question 1 Explanation: 
This patient presents with occasional mood swings, irritability, and appetite changes that are affecting her functioning and relationships, most consistent with premenstrual dysphoric disorder (PMDD). First-line treatment is a selective serotonin reuptake inhibitor (SSRI). The diagnosis of PMDD requires temporal correlation of symptoms with menstruation, with symptom severity being the highest in the week leading to menstruation and resolving soon after menses begin. In order to establish this timing, patient documentation of symptom frequency and menstrual patterns is required. Treatment with an SSRI is first-line, and pyridoxine (vitamin B6) has also been shown to be effective in some cases.
Question 2
A 27-year-old woman is presenting to her physician assistant with a constellation of physical and affective symptoms that she believes are associated with her menstrual cycle. Which of the following is consistent with premenstrual syndrome and does not warrant further testing?
Difficulty swallowing
These symptoms are not consistent with PMS.
Sudden bleeding
These symptoms are not consistent with PMS.
Weight gain
Breast size decrease
These symptoms are not consistent with PMS.
Cold intolerance
These symptoms are not consistent with PMS.
Question 2 Explanation: 
Premenstrual syndrome (PMS) is a constellation of physical and affective symptoms associated with the luteal phase of the female reproductive cycle that remit with the onset of menses or shortly thereafter. Cold intolerance is not a component of the syndrome and would be more consistent with hypothyroidism. PMS is diagnosed based on history and ruling out overlapping conditions such as anemia, endocrine abnormalities, and other psychiatric conditions. Some of the symptoms of PMS include: depression, anxiety, anhedonia, fatigue, headaches, bloating, and weight gain. The symptoms are severe enough to interfere with functioning in social or professional settings. The symptoms resolve for at least 1 week during each menstrual cycle.
There are 2 questions to complete.
Shaded items are complete.

References: Merck Manual · UpToDate

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