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AI-Generated response:

What are the treatments for PMDD?

Answer generated on June 4, 2024

The AI-generated responses are for illustration purposes only and should not be used for medical purposes.

Treatments for premenstrual dysphoric disorder (PMDD) include selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), oral contraceptives, GnRH agonists, and nonpharmacologic therapies.

SSRIs can cause sexual dysfunction, nausea, headache, and insomnia.

SNRIs may cause similar side effects and also increase blood pressure.

Oral contraceptives can increase the risk of thromboembolic events.

GnRH agonists can lead to bone density loss, requiring add-back therapy to mitigate this risk.[1-8]

  • SSRIs such as fluoxetine (20 mg/day orally, can be given continuously or during the luteal phase only) and sertraline (50 mg/day orally, can be adjusted based on response and tolerability) are considered first-line treatments.[1-2][7]

  • SNRIs like venlafaxine are effective, particularly for psychological symptoms, and can be used off-label.[1][4]

  • Oral contraceptives containing drospirenone and ethinyl estradiol (e.g., 3 mg/0.02 mg once daily for 24 days followed by 4 days of inactive tablets) are indicated for women who also desire contraception.[3][5-6][8]

  • GnRH agonists such as leuprolide are reserved for severe cases unresponsive to other treatments and require add-back therapy due to the risk of bone density loss.[1]

  • Nonpharmacologic approaches include lifestyle modifications such as reducing caffeine and sodium intake, increasing exercise, stress management, and cognitive-behavioral therapy.[1]

Additional info

When considering treatment options for PMDD, it is crucial to tailor the approach based on the severity of symptoms and the patient's overall health profile. For instance, while SSRIs are widely used due to their efficacy in alleviating mood symptoms, their side effects like sexual dysfunction and weight changes might be undesirable for some patients. Similarly, while oral contraceptives are beneficial for those seeking both contraception and symptom relief, they are contraindicated in women with a history of thromboembolic disorders.GnRH agonists, although effective, are generally considered a last resort due to significant side effects such as potential bone density loss, highlighting the importance of add-back therapy with estrogen or progesterone to mitigate these effects. Nonpharmacologic treatments can be particularly appealing for individuals looking to avoid medication side effects, focusing on lifestyle adjustments and psychological therapies.It's also important to consider patient preference, lifestyle, and potential compliance issues when selecting a treatment modality, ensuring a holistic approach to managing this complex disorder. Regular follow-up is essential to monitor treatment efficacy and adjust the therapeutic approach as needed.

References

Reference 1

1.

Premenstrual Dysphoric Disorder, Elsevier ClinicalKey Derived Clinical Overview

• Selective serotonin reuptake inhibitors are useful for the treatment of PMDD. Commonly used agents and initial doses are fluoxetine 10 mg/day, sertraline 50 mg/day, paroxetine 10 mg/day, and citalopram 20 mg/day. Many patients will require titration to significantly higher doses to achieve therapeutic benefit. 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. Serotonin-norepinephrine reuptake inhibitors (SNRIs) such as venlafaxine may also be effective in women with predominantly psychological symptoms. • Other useful agents are benzodiazepines (alprazolam 0.25 mg tid prn) and the tricyclic antidepressant clomipramine (25 mg/day as starting dose). • Gonadotropin-releasing hormone (GnRH) agonists are effective in treating patients with PMDD. The 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 B6up 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.

• Reduction in intake of caffeine, refined sugars, or sodium may be helpful in some patients. • Increased aerobic exercise, smoking cessation, alcohol restriction, and regular sleep are often beneficial. • Stress reduction and management will decrease severity of symptoms. • Cognitive-behavior therapy may also be helpful for reducing symptoms.

Premenstrual dysphoric disorder (PMDD) comprises emotional and physical symptoms and functional impairment that lie on the severe end of the continuum of premenstrual symptoms. Women with PMDD have a differential response to normal hormonal fluctuations. This susceptibility may involve the serotonin system, altered sensitivity of the GABA receptor to the neurosteroid allopregnanalone, and altered brain circuitry involving emotional and cognitive functions. Serotonin reuptake inhibitors are considered the first-line treatment. Second-line treatments include oral contraceptives containing drospirenone, other ovulation suppression methods, calcium, chasteberry, and cognitive-behavioral therapy.

Reference 2

2.

Fluoxetine, Elsevier ClinicalKey Drug Monograph Content last updated: March 4, 2024

Indications And Dosage Oral dosage (e.g., Sarafem or other regular capsules, tablets or oral solution) Adult females: 20 mg PO once daily initially, given continuously or during the luteal phase only (i.e., starting a daily dose 14 days prior to the anticipated start of menses through the first full day of menses and repeating with each new cycle). In clinical trials, doses of 20 to 60 mg/day PO were effective, although the 60-mg dose did not provide additional benefit. Doses above 60 mg/day PO have not been evaluated in PMDD. Max: 80 mg/day PO.

Reference 3

3.

Drospirenone; Ethinyl Estradiol; Levomefolate, Elsevier ClinicalKey Drug Monograph Content last updated: May 5, 2024

Indications And Dosage Oral dosage (monophasic product, Beyaz and generics, e.g., Rajani) Adult and Adolescent females: 1 tablet PO once daily; pills should be taken in the order directed on the blister pack. The first 24 pills contain 3 mg drospirenone, 0.02 mg of ethinyl estradiol, and 0.451 mg levomefolate calcium; the last 4 tablets contain 0.451 mg levomefolate calcium. The cycle should be repeated every 28 days. The use of drospirenone; ethinyl estradiol improves many of the symptoms associated with premenstrual complaints, including negative mood, water retention, and increased appetite.

Reference 4

4.

Premenstrual Syndrome, Elsevier ClinicalKey Derived Clinical Overview

• Sertraline, paroxetine, fluoxetine, citalopram, escitalopram are most commonly used, • In 2013 theCochrane Reviewsreported a statistically significant benefit over placebo when taken either continuously or in the luteal phase • Serotonin-norepinephrine reuptake inhibitors (SNRI) such as venlafaxine; use is off-label, but onset of action is quick and has been found to be helpful • Seroquel: Smaller studies • Wellbutrin: Not as effective as the other options • Ulipristal Acetate is a second-generation Selective Progesterone Receptor Modulator (SPRM) that shows promise at low doses (5 mg/day) in ameliorating symptoms of PMDD • Off-label use of Dutasteride to increase local allopregnanolone levels and ameliorate physical and psychologic symptoms of PMDD

Reference 5

5.

Drospirenone; Ethinyl Estradiol, Elsevier ClinicalKey Drug Monograph Content last updated: May 5, 2024

Indications And Dosage Oral dosage (YAZ monophasic formulation and generic equivalents, e.g., Gianvi, Loryna, Nikki, Vestura) Adult and Adolescent females: 1 tablet (containing 3 mg drospirenone and 20 mcg ethinyl estradiol) PO once daily for 24 days, followed by 4 days of non-hormonal, inactive tablets. Repeat cycle every 28 days. Two multicenter, double-blind, randomized, placebo-controlled studies in adult women meeting DSM-IV criteria for PMDD, confirmed by prospective daily ratings of their symptoms, were performed; efficacy was measured using the Daily Record of Severity of Problems scale for the PMDD symptoms of the DSM-IV diagnostic criteria, using a scoring system based on the first 21 items. In both trials, women who received this regimen had statistically significantly greater improvement in their Daily Record of Severity of Problems vs. placebo. Other trials have also reported effectiveness in improving common symptoms of PMDD (negative emotions, food cravings and water retention-related symptoms) vs. placebo. Oral dosage† (off-label indication) (Yasmin monophasic formulation and generic equivalents, e.g., Ocella, Syeda, Zarah)† (off-label indication) Adult and Adolescent females: Not FDA-approved, but clinically studied. 1 tablet (containing 3 mg drospirenone and 30 mcg ethinyl estradiol) PO once daily for 21 days, followed by 7 days of inert, inactive tablets, as directed by the order of the pack. Repeat cycle every 28 days. Data suggest this regimen is effective in improving symptoms of PMDD (food cravings and appetite, acne, negative emotions, etc.).

Reference 6

6.

Food and Drug Administration (DailyMed). LORYNA. 2024. Publish date: January 3, 2024

Indications And Usage 1 INDICATIONS AND USAGE LORYNA (drospirenone and ethinyl estradiol tablets) is an estrogen/progestin COC, indicated for use by women to: Prevent pregnancy. ( 1.1 ) Treat symptoms of premenstrual dysphoric disorder (PMDD) for women who choose to use an oral contraceptive for contraception. ( 1.2 ) Treat moderate acne for women at least 14 years old only if the patient desires an oral contraceptive for birth control. ( 1.3 ) 1.1 Oral Contraceptive LORYNA (drospirenone and ethinyl estradiol tablets) are indicated for use by women to prevent pregnancy. 1.2 Premenstrual Dysphoric Disorder (PMDD) LORYNA (drospirenone and ethinyl estradiol tablets) is also indicated for the treatment of symptoms of premenstrual dysphoric disorder (PMDD) in women who choose to use an oral contraceptive as their method of contraception. The effectiveness of LORYNA (drospirenone and ethinyl estradiol tablets) for PMDD when used for more than three menstrual cycles has not been evaluated. The essential features of PMDD according to the Diagnostic and Statistical Manual-4th edition (DSM-IV) include markedly depressed mood, anxiety or tension, affective lability, and persistent anger or irritability. Other features include decreased interest in usual activities, difficulty concentrating, lack of energy, change in appetite or sleep, and feeling out of control. Physical symptoms associated with PMDD include breast tenderness, headache, joint and muscle pain, bloating and weight gain. In this disorder, these symptoms occur regularly during the luteal phase and remit within a few days following onset of menses; the disturbance markedly interferes with work or school, or with usual social activities and relationships with others. Diagnosis is made by healthcare providers according to DSM-IV criteria, with symptomatology assessed prospectively over at least two menstrual cycles. In making the diagnosis, care should be taken to rule out other cyclical mood disorders.

Reference 7

7.

Food and Drug Administration (DailyMed). SERTRALINE. 2024. Publish date: March 1, 2024

Clinical Studies The mean duration of PMDD symptoms was approximately 10.5 years in both studies. Patients taking oral contraceptives were excluded from these trials; therefore, the efficacy of sertraline in combination with oral contraceptives for the treatment of PMDD is unknown. Efficacy was assessed with the Daily Record of Severity of Problems (DRSP), a patient-rated instrument that mirrors the diagnostic criteria for PMDD as identified in the DSM-IV, and includes assessments for mood, physical symptoms, and other symptoms. Other efficacy assessments included the Hamilton Rating Scale for Depression (HAMD-17), and the Clinical Global Impression Severity of Illness (CGI-S) and Improvement (CGI-I) scores. In Study PMDD-1, involving 251 randomized patients, (n=125 on sertraline and n=126 on placebo), sertraline treatment was initiated at 50 mg/day and administered daily throughout the menstrual cycle. In subsequent cycles, sertraline was titrated in 50 mg increments at the beginning of each menstrual cycle up to a maximum of 150 mg/day on the basis of clinical response and tolerability. The mean dose for completers was 102 mg/day. Sertraline administered daily throughout the menstrual cycle was statistically significantly more effective than placebo on change from baseline to endpoint on the DRSP total score, the HAMD-17 total score, and the CGI-S score, as well as the CGI-I score at endpoint. In Study PMDD-2, involving 281 randomized patients, (n=142 on sertraline and n=139 on placebo), sertraline treatment was initiated at 50 mg/day in the late luteal phase (last 2 weeks) of each menstrual cycle and then discontinued at the onset of menses (intermittent dosing). In subsequent cycles, patients were dosed in the range of 50-100 mg/day in the luteal phase of each cycle, on the basis of clinical response and tolerability. Patients who received 100 mg/day started with 50 mg/day for the first 3 days of the cycle, then 100 mg/day for the remainder of the cycle. The mean sertraline dose for completers was 74 mg/day.

Reference 8

8.

Food and Drug Administration (DailyMed). Nikki. 2023. Publish date: December 4, 2023

Indications And Usage 1 INDICATIONS AND USAGE Nikki (drospirenone and ethinyl estradiol) (Nikki (drospirenone and ethinyl estradiol) tablets USP) is a combination of drospirenone, a progestin, and ethinyl estradiol, an estrogen, indicated for use by females of reproductive potential to: Prevent pregnancy. ( 1.1 ) Treat symptoms of premenstrual dysphoric disorder (PMDD) for females of reproductive potential who choose to use an oral contraceptive for contraception. ( 1.2 ) Treat moderate acne for women at least 14 years old only if the patient desires an oral contraceptive for birth control. ( 1.3 ) 1.1 Oral Contraceptive Nikki (drospirenone and ethinyl estradiol)™ (Nikki (drospirenone and ethinyl estradiol) tablets USP), 3 mg/0.02 mg is indicated for use by females of reproductive potential to prevent pregnancy. 1.2 Premenstrual Dysphoric Disorder (PMDD) Nikki (drospirenone and ethinyl estradiol) (Nikki (drospirenone and ethinyl estradiol) tablets USP), 3 mg/0.02 mg is also indicated for the treatment of symptoms of premenstrual dysphoric disorder (PMDD) in females of reproductive potential who choose to use an oral contraceptive as their method of contraception. The effectiveness of Nikki (drospirenone and ethinyl estradiol) (Nikki (drospirenone and ethinyl estradiol) tablets USP), 3 mg/0.02 mg for PMDD when used for more than three menstrual cycles has not been evaluated. The essential features of PMDD according to the Diagnostic and Statistical Manual-4th edition (DSM-IV) include markedly depressed mood, anxiety or tension, affective lability, and persistent anger or irritability. Other features include decreased interest in usual activities, difficulty concentrating, lack of energy, change in appetite or sleep, and feeling out of control.

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