Premenstrual Dysphoric Disorder Medication

Updated: Sep 15, 2021
  • Author: Thwe T Htay, MD, FACP; Chief Editor: Ana Hategan, MD, FRCPC  more...
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Medication Summary

The goal of pharmacotherapy is to relieve symptoms. Agents used in the management of premenstrual dysphoric disorder (PMDD) include vitamins and minerals, diuretics, nonsteroidal anti-inflammatory drugs (NSAIDs), antidepressants, beta-blockers, anxiolytics, and contraceptives.


Nutritionals, Other

Class Summary

Vitamins and minerals have been used for PMDD with varying success rates, as described in the literature.

Pyridoxine (Pyri 500, Vitamin B6, Neuro-K-250 T.D.)

Pyridoxine is involved in the synthesis of gamma-aminobutyric acid (GABA) within the central nervous system (CNS).

Calcium carbonate (Caltrate 600, TUMS, Oysco 500, Rolaids Extra Strength)

Calcium supplementation during the luteal phase has proven beneficial with regard to bloating, pain, mood, and food cravings.



Class Summary

The ability of the androgens to inhibit luteinizing hormone (LH) and follicle-stimulating hormone (FSH) release may have a positive effect in the treatment of PMDD.


Danazol is a synthetic steroid analogue with strong antigonadotropic activity (ie, inhibition of LH and FSH) and weak androgenic action.


Aldosterone Antagonists, Selective

Class Summary

Diuretics are widely used for PMDD, on the assumption that many symptoms are secondary to fluid retention.

Spironolactone (Aldactone, CaroSpir)

Spironolactone competes with aldosterone for receptor sites in distal renal tubules, increasing water excretion while retaining potassium and hydrogen ions.

Metolazone (Zaroxolyn)

Metolazone is a thiazide diuretic with a reported beneficial effect in PMDD. It increases excretion of sodium, water, potassium, and hydrogen ions by inhibiting reabsorption of sodium in distal tubules.


Nonsteroidal Anti-inflammatory Drugs (NSAIDs)

Class Summary

NSAIDs are reported to improve some physical and mental symptoms in PMDD.

Naproxen (Aleve, Naprelan, Naprosyn, Mediproxen)

Naproxen is reported to improve mood changes and headache in PMDD. Used for the relief of mild to moderate pain. It inhibits inflammatory reactions and pain by decreasing the activity of the enzyme cyclo-oxygenase, which results in prostaglandin synthesis.

Mefenamic acid (Ponstel)

Mefenamic acid is reported to improve premenstrual symptoms, except breast pain. Inhibits inflammatory reactions and pain by decreasing the activity of cyclooxygenase, thereby decreasing prostaglandin synthesis. Compared with other NSAIDs, it is associated with a higher incidence of diarrhea.


Antidepressants, Other

Class Summary

Antidepressants are reported to have positive effects on 1 or more symptoms of PMDD as compared with placebo. Antidepressant therapy is indicated if PMDD symptoms of depression are moderate to severe.

Bupropion (Wellbutrin, Aplenzin, Fortivo XL)

Bupropion inhibits neuronal dopamine reuptake, in addition to being a weak blocker of serotonin and norepinephrine reuptake.

Clomipramine (Anafranil)

Clomipramine affects serotonin uptake. When converted into its metabolite, desmethyl clomipramine, it affects norepinephrine uptake.

Nortriptyline (Pamelor)

Nortriptyline inhibits reuptake of serotonin, norepinephrine, or both by the presynaptic neuronal membrane.

Fluoxetine (Sarafem, Prozac)

Fluoxetine selectively inhibits presynaptic serotonin reuptake, with minimal or no effect on reuptake of norepinephrine or dopamine.

Sertraline (Zoloft)

Sertraline selectively inhibits presynaptic serotonin reuptake.

Paroxetine (Paxil, Pexeva)

Paroxetine selectively inhibits presynaptic serotonin reuptake. It is reported to have positive effects on 1 or more symptoms of PMDD as compared with placebo.


Beta-Blockers, Beta-1 Selective

Class Summary

A double-blinded study found the beta-adrenergic blocking agent atenolol to improve irritability. However, a placebo-controlled study of prospectively diagnosed patients found no improvement with atenolol.

Atenolol (Tenormin)

Atenolol selectively blocks beta1 receptors, with little or no effect on beta2 types.


Antianxiety Agents

Class Summary

Anxiolytics are reported to have positive effects on 1 or more symptoms of PMDD as compared with placebo. They should be used in the management of PMDD if anxiety is the prominent symptom, with dysphoria occurring secondarily.

Alprazolam (Xanax)

Alprazolam reduces depression, irritability, and anxiety in PMDD.


Buspirone is a serotonin agonist with serotonergic neurotransmission and some dopaminergic effects in the CNS.



Class Summary

Contraceptives reduce secretion of LH and FSH from the pituitary by decreasing the amount of gonadotropin-releasing hormone (GnRH).

Ethinyl estradiol and drospirenone (YAZ, Zarah, Ocella, Loryna, Vestura, Syeda)

This formulation is an oral contraceptive containing ethinyl estradiol 20 µg and drospirenone 3 mg. It is indicated for PMDD in women who choose to use an oral contraceptive as their method of contraception.

Norethindrone acetate/ethinyl estradiol (Ortho-Novum, Nortrel, Cyclafem, Wera)

Norethindrone acetate and ethinyl estradiol are used as an oral contraceptive. The formula is used in women who choose to use an oral contraceptive as their method of contraception.