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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, MDDTM 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.
CONTRAINDICATIONS
Hypersensitivity: Hypersensitivity to vortioxetine or any component of the TRINTELLIX formulation. Hypersensitivity reactions including anaphylaxis, angioedema, and urticaria have been reported in patients treated with TRINTELLIX.
Monoamine Oxidase Inhibitors (MAOIs): Do not use MAOIs intended to treat psychiatric disorders with TRINTELLIX or within 21 days of stopping treatment with TRINTELLIX, due to an increased risk of serotonin syndrome. Do not use TRINTELLIX within 14 days of stopping an MAOI intended to treat psychiatric disorders.
Linezolid and Methylene Blue: Do not start TRINTELLIX in a patient being treated with MAOIs such as linezolid or intravenous methylene blue, due to an increased risk of serotonin syndrome.
WARNINGS AND PRECAUTIONS
Suicidal Thoughts and Behaviors in Adolescents and Young Adults: Monitor all antidepressant-treated patients for clinical worsening and emergence of suicidal thoughts and behaviors, especially during the initial few months of drug therapy, and at times of dosage changes. Counsel family members or caregivers of patients to monitor for changes in behavior and to alert the healthcare provider. Consider changing the therapeutic regimen, including possibly discontinuing TRINTELLIX, in patients whose depression is persistently worse, or who are experiencing emergence of suicidal thoughts and behaviors. In pooled analyses of placebo- controlled trials of antidepressants, the incidence of suicidal thoughts and behaviors in antidepressant-treated patients ages 24 and younger was greater than in placebo-treated patients.
Serotonin Syndrome: Serotonergic antidepressants, including TRINTELLIX, can precipitate serotonin syndrome, a potentially life-threatening condition. The risk is increased with concomitant use of other serotonergic drugs (including triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, meperidine, methadone, buspirone, amphetamines, and St. John’s Wort) and with drugs that impair metabolism of serotonin, that is, MAOIs. Serotonin syndrome signs and symptoms may include mental status changes (for example, agitation, hallucinations, delirium, and coma), autonomic instability (for example, tachycardia, labile blood pressure, dizziness, diaphoresis, flushing, hyperthermia), neuromuscular symptoms (for example, tremor, rigidity, myoclonus, hyperreflexia, incoordination), seizures, and gastrointestinal symptoms (for example, nausea, vomiting, diarrhea). Monitor all patients taking TRINTELLIX for the emergence of serotonin syndrome. Discontinue treatment with TRINTELLIX and any concomitant serotonergic agents immediately if the above symptoms occur, and initiate supportive symptomatic treatment. If concomitant use of TRINTELLIX with other serotonergic drugs is clinically warranted, inform patients of the increased risk for serotonin syndrome and monitor for symptoms.
Increased Risk of Bleeding: The use of drugs that interfere with serotonin reuptake inhibition, including TRINTELLIX, may increase the risk of bleeding events, including but not limited to gastrointestinal. Concomitant use of aspirin, nonsteroidal anti- inflammatory drugs (NSAIDs), warfarin, and other anticoagulants may add to this risk. Inform patients about the increased risk of bleeding when TRINTELLIX is coadministered with NSAIDs, aspirin, or other drugs that affect coagulation or bleeding.
Exposure to SSRIs or SNRIs, particularly in the month before delivery, has been associated with a less than 2-fold increase in the risk of postpartum hemorrhage.
Activation of Mania/Hypomania: In patients with bipolar disorder, treating a depressive episode with TRINTELLIX or another antidepressant may precipitate a mixed/manic episode. Prior to initiating treatment with TRINTELLIX, screen patients for any personal or family history of bipolar disorder, mania, or hypomania.
Discontinuation Syndrome: Adverse reactions have been reported upon abrupt discontinuation of treatment with TRINTELLIX at doses of 15 mg/day and 20 mg/day. A gradual reduction in dosage rather than abrupt cessation is recommended whenever possible.
Angle-Closure Glaucoma: The pupillary dilation that occurs following use of many antidepressant drugs, including TRINTELLIX, may trigger an angle-closure attack in a patient with anatomically narrow angles who does not have a patent iridectomy.
Hyponatremia: Hyponatremia has occurred as a result of treatment with serotonergic drugs, including TRINTELLIX, and in many cases appears to be the result of the syndrome of inappropriate antidiuretic hormone secretion (SIADH). Elderly patients and patients taking diuretics or who are otherwise volume-depleted can be at greater risk. Symptoms of hyponatremia include headache, difficulty concentrating, memory impairment, confusion, weakness, and unsteadiness, which can lead to falls. More severe and/or acute cases have included hallucination, syncope, seizure, coma, respiratory arrest, and death. Discontinue TRINTELLIX in patients with symptomatic hyponatremia and institute appropriate medical intervention.
Sexual Dysfunction: Use of serotonergic antidepressants, including TRINTELLIX, may cause symptoms of sexual dysfunction. In male patients, serotonergic antidepressant use may result in ejaculatory delay or failure, decreased libido, and erectile dysfunction. In female patients, use may result in decreased libido and delayed or absent orgasm.
ADVERSE REACTIONS
The most commonly observed adverse reactions for TRINTELLIX in 6- to 8-week placebo-controlled studies (incidence greater than or equal to 5% and at least twice the rate of placebo) were: nausea, constipation, and vomiting.
DRUG INTERACTIONS
Concomitant administration of TRINTELLIX and strong CYP2D6 inhibitors or strong CYP inducers may require a dose adjustment of TRINTELLIX.
PREGNANCY
Exposure to serotonergic antidepressants, including TRINTELLIX, in late pregnancy may increase the risk for neonatal complications requiring prolonged hospitalization, respiratory support, and tube feeding, and/or persistent pulmonary hypertension of the newborn (PPHN). Monitor neonates who were exposed to TRINTELLIX in the third trimester for PPHN and drug discontinuation syndrome. Use of TRINTELLIX in the month before delivery may be associated with an increased risk of postpartum hemorrhage.
Please see Full Prescribing Information, including Boxed WARNING regarding Suicidal Thoughts and Behaviors, by clicking on the link below this video.
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.
US-VOR-1683v1.0 05/25
