A Look at MDD: Symptoms, TESD, and Treatment Strategies

Paid content from Takeda Pharmaceuticals

Please click for Full Prescribing Information

Hello, I’m Dr. Leslie Citrome, Clinical Professor of Psychiatry and Behavioral Sciences at New York Medical College in Valhalla, New York. I’m pleased to introduce this two-part video series with Psychiatric Times, which is sponsored content from Takeda Pharmaceuticals, where we’ll delve into the complexities of Major Depressive Disorder, or MDD, and approaches to treating this disorder. I'll also be exploring Treatment-Emergent Sexual Dysfunction, or TESD, emphasizing the importance of ongoing conversations with patients to ensure their treatment aligns with their needs.

As a practicing psychiatrist for more than 35 years, I’ve dedicated much of my career to understanding and treating individuals with MDD. Everyone experiences MDD differently; and, to understand the disorder, we must explore the multiple symptoms that define MDD.¹

As we know, per the American Psychiatric Association’s Diagnostic and Statistical Manual now in its fifth edition and additionally revised, the DSM-5-TR^TM, MDD manifests as a complex combination of five or more symptoms, present nearly every day during the same 2-week period and represent a change from previous functioning. At least one of these symptoms must be depressed mood or loss of interest or pleasure in all, or almost all, activities.¹

Other symptoms include¹:

• significant weight loss or weight gain, or change in appetite
• insomnia or hypersomnia
• psychomotor agitation or retardation
• fatigue or loss of energy
• feelings of worthlessness or excessive or inappropriate guilt
• difficulty thinking or concentrating, or indecisiveness
• and, recurrent thoughts of death or suicidal actions or ideation.

Variability in symptoms is one of the key reasons why MDD is different for every person.¹ There is no one-size-fits-all approach to treating MDD, and health care providers need to be adaptable to address the specific challenges of each individual. That’s why I also find it especially important to use rating scales, such as the Patient Health Questionnaire, or PHQ-9, to assess the severity of depressive symptoms in adults and the effects of treatment over time.

I want to take this opportunity to talk about one prescription medication indicated to treat MDD in adults that has multimodal pharmacologic activity. It’s called Trintellix^®, also known as vortioxetine. Trintellix is available as 5 mg, 10 mg, and 20 mg tablets.²

TRINTELLIX has a Boxed Warning for suicidal thoughts and behaviors.² Antidepressants increased the risk of suicidal thoughts and behaviors in pediatric and young adult patients in short-term studies. Closely monitor all antidepressant-treated patients for clinical worsening, and for emergence of suicidal thoughts and behaviors. TRINTELLIX is not approved for use in pediatric patients.

Please listen for additional Important Safety Information later in this video, and see the Full Prescribing Information by clicking on the link below this video.

Trintellix monotherapy was shown to reduce the overall symptoms of MDD across 6 short-term clinical studies, which were measured by the total score of the Hamilton Depression 24-item Rating Scale or the Montgomery-Asberg Depression Rating Scale.² Those six clinical studies were randomized, double-blind, and placebo-controlled, over a 6- to 8-week duration. Patients were given a once-daily dosage of Trintellix, ranging from 5 mg to 20 mg.

The most common adverse reactions with an incidence of 5% or more and at least twice the rate of placebo in the 6- to 8-week studies were nausea, constipation, and vomiting.

As you can see on the screen, no other MDD medication is thought to work exactly like Trintellix. Trintellix is the first and only compound with this combination of pharmacologic activity. The mechanism of the antidepressant effect of Trintellix is not fully understood, but it is thought to be related to its enhancement of serotonergic activity in the central nervous system through inhibition of the reuptake of serotonin (5-HT).² It also has several other activities including 5-HT3 receptor antagonism and 5-HT1A receptor agonism. The contribution of these activities to the antidepressant effect of Trintellix has not been established.

Trintellix strongly inhibits the serotonin transporter, or SERT, and has strong affinities for 5 other serotonin receptors.

For serotonergic antidepressants, including Selective Serotonin Reuptake Inhibitors, or SSRIs, sexual dysfunction is not an uncommon side effect.³ In a meta-analysis of several studies, treatment-emergent sexual dysfunction, or TESD, was found to affect 25% to 80% of patients taking an antidepressant. Those experiencing TESD due to their antidepressant may have trouble reaching and achieving orgasm or ejaculating and, in some cases, may experience a reduction in libido, or the ability to achieve and maintain an erection or vaginal lubrication.

In a clinical study comparing Trintellix to escitalopram (another antidepressant also known as Lexapro^®), data showed that for MDD patients with SSRI-induced TESD from citalopram, paroxetine, or sertraline, a switch to Trintellix resulted in statistically superior improvement in sexual side effects compared to escitalopram (as measured by the Changes in Sexual Functioning Questionnaire Short-Form (CSFQ-14)) while both drugs maintained the patients’ prior antidepressant response.^2,4 Common adverse events, defined as events with an incidence of at least 5% for Trintellix, were nausea, headache, dizziness, and generalized pruritus.⁴

In addition to this head-to-head study, sexual side effects were prospectively assessed using the Arizona Sexual Experiences Scale in patients without sexual dysfunction at baseline in seven placebo-controlled trials.² TESD was reported in both males and females at Trintellix doses ranging from 5 mg to 20 mg per day, as well as in patients on placebo.

As we continue to explore and learn more about MDD and the treatment options available to patients, it is clear that effective care requires a true partnership between health care providers and patients, addressing important topics like overall symptom relief and side effects such as TESD. Developing individualized approaches is essential, with clinicians and patients working closely together to address each person’s experience with MDD.

Please continue listening for additional Important Safety Information, and click the link beneath this video for the Full Prescribing Information. I also encourage you to visit www.TrintellixHCP.com for more expert insights. The site also includes information about how your eligible patients can enroll in the Trintellix Savings Program.

In the next video of this series, we’ll dive into speed of processing, an aspect of cognitive function that may be impaired in MDD. But first, please listen to the additional Important Safety Information.

¹ American Psychiatric Association. Depressive disorders. In: Diagnostic and Statistical Manual of Mental Disorders. 5th edition (DSM-5®). Arlington, VA: American Psychiatric Association; 2013:155‑188.
² TRINTELLIX (vortioxetine) prescribing information. Takeda Pharmaceuticals. 2023.
³ Serretti A, Chiesa A. Int Clin Psychopharmacol. 2011;26(3):130-140.
⁴ Jacobsen PL, Mahableshwarkar AR, Chen Y, Chrones L, Clayton AH. J Sex Med. 2015;12(10):2036‑2048.