Questions and answers

1. How common is major depressive disorder (MDD)?

Approximately 21 million US adults aged ≥18 years experienced a major depressive episode* in 2020.1†

20.6% of adult participants in a national survey were estimated to have experienced MDD at some point in their lives.2‡

*A major depressive episode is a primary component of MDD, but differs from MDD in that MDD cannot be better explained by a psychotic disorder and there has never been a manic or hypomanic episode.3

NSDUH 2020 prevalence estimates based on sample size of N = 29,950.1

Report of 2012-2013 National Epidemiologic Survey on Alcohol and Related Conditions III (N= 36,309).2

2. How has the COVID-19 pandemic affected rates of depression?

The COVID-19 pandemic appears to have increased symptoms of mental illness, including depression. As of 2020, there was a 3-fold increase in symptoms of depression compared to pre-COVID levels in 2018.4

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3. What is the daily impact of depression?

Depression is a leading cause of disability worldwide.5 In the National Health and Nutrition Examination Survey (NHANES), 80% percent of people with depression reported that their symptoms made it difficult to work, maintain a home, and be socially active. Patients with major depressive disorder (MDD) are approximately 2 times as likely to have missed two or more weeks of work in a year due to illness compared to people without a mood disorder.6

4. What is the role of neurotransmitters other than monoamines in depression?

Recent evidence suggests that the non-monoaminergic neurotransmitters, GABA and glutamate, may play a role in depression. GABA and glutamate exert intrinsic and extrinsic control over the flow of information in the brain.7,8

5. What is the role of GABA in depression?

Preclinical and clinical studies have indicated that deficient GABAergic neurotransmission may play a role in the pathophysiology of depression.7 It has been hypothesized that a depressive episode may result when excitatory signaling in the brain is not properly balanced by inhibitory GABAergic signaling.7-10

6. What is the role of glutamate in depression?

Glutamate is an excitatory neurotransmitter that affects the intrinsic and extrinsic flow of information in the brain. There is evidence that glutamate-mediated neurotransmission may be altered in depression.7

7. What is the STAR*D study?

The Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study enrolled 4041 adult outpatients with major depressive disorder (MDD) to evaluate outcomes of 4 successive acute treatment steps. In treatment step 1, patients (n=3671) received antidepressant monotherapy. Those who did not achieve remission (Quick Inventory of Depressive Symptomatology (Self Report)-16 item [QIDS-SR16] score ≤5) or were unable to tolerate treatment were eligible to move to the next step. Steps 2-4 included several switch and augmentation choices. Patients who benefited from treatment could enter a 12-month naturalistic follow-up phase.11

8. What did the STAR*D study find regarding the efficacy of antidepressants?

The results of the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study found that approximately two-thirds of patients failed to achieve remission on first-line antidepressant therapy. For the 36% who did achieve remission, mean time to remission was 6.3 weeks.11

9. What is the average response rate to antidepressants?

In a meta-analysis of 182 clinical trials of antidepressants used as monotherapy, nearly half of patients with major depressive disorder (MDD) failed to respond. The pooled non-response rate was 46.2%, with response defined as a 50% or greater reduction in the Hamilton Depression Rating Score (HDRS) or Montgomery-Åsberg Depression Rating Scale (MADRS) scores from baseline or a Clinical Global Impressions (CGI) Scale scores less than 3 at final visit.12

10. Is there a correlation between time to antidepressant response and long-term success?

Earlier response to an antidepressant may indicate a higher likelihood of achieving remission. A meta-analysis of 17 randomized, double-blind trials of 14,779 patients with major depressive disorder (MDD) found that there was a 6x greater likelihood of remission for patients with had ≥20% reduction in their Hamilton Depression Rating Scale (HAMD) or Montgomery- Åsberg Depression Rating Scale (MADRS) scores at day 7 or day 14 of treatment.13

11. How long do SSRI antidepressant side effects typically persist?

A 6-month telephone study found that typical side effects of selective serotonin reuptake inhibitor (SSRI) antidepressants—such as sexual dysfunction, drowsiness, insomnia, and weight gain—often persisted for 3 months or more.14 Up to 35.7% of patients who discontinued antidepressant therapy early (within 2 months) cited side effects as a reason.15