Albuquerque, NM — Premenstrual Dysphoric Disorder (PMDD) poses a greater risk for anxiety and depression. Ketamine may be a potential therapy for you.

Symptoms of PMDD:

  1. Physical: It’s a general feeling of being sick. Your head, muscles, or joints ache. Your breasts are tender, and you feel bloated. 
  2. Psychological: You may feel depressed, sad, or worthless. You may have bouts of mood swings, irritability, or increased anxiety.
  3. Behavioral: You may lack the energy and interest to do your usual activities. You skip a meal or binge eat as your appetite changes. You may experience either oversleeping or insomnia. There’s just no way for you to control the situation and you feel overwhelmed.

Prevalence of psychological symptoms in PMDD:

In 1997, researchers conducted a study to determine the link between PMDD and psychological or mood disorders. The researcher noted women with PMDD have similar symptoms to other women suffering from psychological or mood disorders. But this doesn’t mean they can share the same kind of therapies. 

The researcher further stressed differentiating PMDD  from mood disorders should be done in terms of intervention options.  Biological and cognitive conditions and response to interventions are criteria for decisions regarding options.

In 2013, the Diagnostic and Statistics Manual of Mental Disorders, 5th Edition (DSM-5) listed PMDD as a separate item under Depressive Disorders with a different criterion for diagnosis, depending on the severity of symptoms.

But a study reveals the existence of comorbidity with mood disorders among teenagers and young adults. Among these comorbidities, anxiety disorder topped the rank at 47.4%.  Other mood disorders followed with a status of  22.9%. The remaining 28.4% was somatoform, a mental disorder with physical manifestations, and 26.5% had no other mental disorder.

In a later study, the most frequent PMDD symptom was irritability or anger among 276 women under DSM-IV criteria for PMDD.  Anxiety, lethargy, and mood swings followed irritability or anger.

Depressive symptoms in PMDD:

Depression, anxiety, and irritability are the most studied PMDD symptoms because women with PMDD consistently display these mood disorders.

  • Researchers interviewed nine women in a two-year pilot study. They found out PMDD posed a risk for major depressive symptoms. They noted  PMDD leads to the onset of major depressive disorder. 
  • A study aimed to assess and determine the role of these mood symptoms in the diagnosis of PMDD. Sixty-seven women with PMDD and 75 other women answered comprehensive questionnaires. The results show women with PMDD exhibited heightened mood symptoms. Depression ranked as the most prominent among the three mood disorders.
  • Symptoms of PMD and PMDD overlap, and researchers correlated these with depression. They studied 116 women aged 18 to 40 years old. They found out  46.6% of the women with depressive symptoms had major depression. The study further reveals PMS and PMDD link to the diagnosis of major depression. Moreover,  the gravity of PMS and the existence of PMDD increased depression.

Thus, researchers in another study highlighted clinicians’ need to assess PMDD with major depressive disorder carefully. They noted women with PMDD and major depression required future studies to identify more appropriate management strategies. 

What causes psychological symptoms in PMDD?

 Researchers attribute the role of neurotransmitters in the brain to the psychological symptoms of PMDD. These neurotransmitters are serotonin, gamma-aminobutyric acid or GABA, glutamate, and beta-endorphins. 

Serotonin is involved with mood regulation. During the premenstrual or luteal phase, there is a decrease in serotonin levels, which results in a bad mood. GABA levels decrease as well, but PMDD connects to the increase in glutamate levels,  PMDD. Serotonin, though, as a modulator leads to an increase in GABA and a decrease in glutamate.

  Selective serotonin reuptake inhibitors and glutamate-targeting antidepressants, having been extensively studied,  are effective in treating PMDD. Ketamine’s mechanism of action involves serotonin, GABA, and glutamate.

Selective Serotonin Reuptake Inhibitors (SSRIs) 

SSRIs, which act as a mood booster,  are known to increase serotonin levels in the brain. Participants received a continuous dose of SSRI during the luteal phase. The review established SSRIs as an effective first-line management of PMDD. Sertraline, an SSRI antidepressant, has been shown to be effective  as therapy for PMDD.

SSRI was significantly more effective than placebo. Another SSRI antidepressant, fluoxetine, effectively treated mood,  physical, and social symptoms associated with PMDD. SSRI’s response rate to treat PMDD is high as it targets irritability, mood swings, and emotional lability.

Role of ketamine in serotonin 1B receptors:

Ketamine may be a potential therapy for PMDD as it interacts with serotonin in the brain like SSRIs. Low levels of serotonin in the brain manifests in severe depression. In an experiment, researchers saw an increase in serotonin turnover in the rat brain after ketamine administration. Using Positron Emission Testing (PET) molecular imaging, a study reveals that ketamine boosted serotonin activity in monkeys’ brains. 

In the latest 2020 study, the number of serotonin 1B receptors increased with the administration of ketamine. Researchers also found out ketamine worked among SSRI-resistant people with major depressive disorder. 

Gamma-Aminobutyric acid or GABA

GABA has a possible role in PMDD. Some progesterone metabolites, tested on mice,  interact with GABA A receptors. Evidence suggests the importance of the GABA A receptor in the cause and potential management for mood disorders, such as PMDD. 

Preliminary findings in another study suggest the abnormal levels of GABA+ and glutamate/mine are associated with women with PMDD.

Serotonin reuptake inhibitors affect enzymes that create progesterone metabolites. The SSRIs modulate GABA A receptors. SSRIs increased GABA concentrations in the brain of people with depression as a primary action

Role of ketamine in gamma-aminobutyric acid: 

People with depressive disorder may have altered levels of GABA A and glutamate in their brains. Ketamine reversed these neurochemical or physiological instabilities. Ketamine increased GABA A receptors in the brain, which leads to ketamine’s anti-depressive effect.

Glutamate 

Changes in glutamate levels result from hormonal fluctuations during the menstrual period. Lower levels of glutamate lead to depressive symptoms experienced by women with PMDD. 

Role of ketamine in glutamate: Depressive symptoms during PMDD are associated with low glutamate levels in the brain. Ketamine increases glutamate. Thus, infusing ketamine in the onset of PMDD symptoms may ease your mood and depressive symptoms.

  • Researchers proposed ketamine as a fast-acting antidepressant due to its effect on the glutamate N-methyl-D-aspartate receptor. 
  • Ketamine activates glutamate in the prefrontal of the brain as a key mechanism. This mechanism contributes to its temporary psychomimetic and sustained long-lasting antidepressant effects. 
  • Estrogen and ketamine showed an additive effect on AMPA receptors, which may have a role in ketamine’s therapeutic response in major depressive disorders. A subtype of ionotropic glutamate, the AMPA receptor,  imitates the effects of glutamate.

Interventions for PMDD 

PMDD negatively impacts your life due to its physical, psychological, and behavioral symptoms. The therapies available for you are SSRIs, hormonal therapy, psychotherapy, and supplements. Other therapies include proper diet or nutrition and exercise.

SSRIs treat PMDD with psychological or mood symptoms. SSRIs are fast-acting. They are effective and significantly improve psychological symptoms at the luteal phase of women with PMDD. It also enhanced the women’s quality of life. 

Ketamine interacts with serotonin in the brain. Moreover, ketamine helps moderate GABA A receptors’ activity and increases glutamate production, which has abnormal levels in PMDD. Best of all, people with major depressive disorder, who are resistant to SSRIs, can receive Ketamine.

Ketamine IV infusion, a potential therapy for PMDD

Ketamine’s mechanism of action is complex, but studies have supported its antidepressant effects. Ketamine IV infusion for PMDD can be a promising therapy to relieve your mood symptoms.  Consult with us on the appropriate intervention for you. Or, visit us at the Injection and Infusion Clinic of ABQ for any ketamine-related concerns.

More than 2,000 infusions have been given safely by our ketamine-certified staff since 2017.

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