What is Trintellix?
Trintellix is the name brand for a drug called vortioxetine. It is classed as an “atypical antidepressant,” and a “serotonin modulator and stimulator.”
The mechanism of action is unknown. It is believed to interfere with natural neurochemicals in the human body by blocking certain receptor sites along the central nervous system. This is believed to elevate levels of certain neurotransmitters, such as serotonin. The FDA says it is not known what effect that may have on depression though drug advertisements suggest otherwise.
Positron Emission Topography (PET) studies have been used in vortioxetine drug studies. In PET studies, a person is injected with a radioactive “tracer” so that changes can be monitored and graphed through a scanning device that produces images of blood flow, changes to glucose, and other internal physical changes. But mental changes were not part of these studies. The label for Trintellix says there is no clear explanation for the drug’s antidepressant effect.
Other research has questioned the veracity of the claim that low serotonin is the cause of depression, and reasoning that drugs that manipulate serotonin are effective antidepressants. The idea that a drug that can boost serotonin and fix depression is something of a controversial discussion that has yet worked well for the industry. No drug creates serotonin.
The important point is that after neurochemicals are suspended or blocked, as antidepressants are believed to do, the neurochemicals become subject to deterioration and are lost. This in fact could result in a serotonin deficiency over time and may explain some of the long-term effects of antidepressants that block serotonin and/or other neurochemicals so manipulated.
What is Trintellix Prescribed to Treat?
According to the drug label, Trintellix is approved for the treatment of MDD in adults. Its use in children has not been studied or evaluated. Major Depressive Disorder is described in the American Psychology Association dictionary as:
“a mood disorder characterized by persistent sadness and other symptoms of a major depressive episode but without accompanying episodes of mania or hypomania or mixed episodes of depressive and manic or hypomanic symptoms, included in DSM-IV-TR, DSM-5, andDSM-5-TR. Also called major depression.” ~ APA Medical Dictionary
Further in this article, the efficacy of drug-based treatments as well as non-drug-based treatments will be explored.8,9
Overview of Trintellix Long-Term Effects, Risks, Benefits
The vast majority of pre-marketing Trintellix drug trials were short-term. As a result, there was sparse documentation on long-term Trintellix effects at the time the drug was approved for sale. There is not a whole lot more information that can be found today, more than a decade since the drug’s release. The adverse events that occurred during drug trials that persisted for more than the 8 or 12 week time period would then need to be classified as long-term effects. 
As would side effects that have been reported as persisting, throughout the post-marketing years. But there is little in the way of long-term trials to draw information from.
In 2019, Denmark researchers compiled a massive review of the long-term side effects that persisted in persons after taking serotonergic medications. Similar to Prozac and other SSRIs and SNRIs, Trintellix is a medication which suppresses the reuptake of serotonin.
These researchers found that short-term trials systematically exaggerated the benefits and underestimated the harms of serotonin reuptake inhibitors, and found the drug trial data unreliable. They also point out the fact that though the drug trials were short-lived, many patients continue taking these medications for years. So the research team decided to take a closer look at how more than 15,000 patients were doing at 9 years after they finished treatment with a serotonergic drug. Using several parameters and observational studies for their assessment, they found that the people who had not been on serotonergic medication or used other means to address major depressive symptoms did better than the people who had taken psychiatric medication.
The following data is taken from the FDA drug label, as well as manufacturers prescribing guidelines, and additional research studies where mentioned.1,2,4-6
Examples of long-term benefits:
- One maintenance drug trial (28 weeks long) showed that some patients taking Trintellix experienced longer times between recurring episodes of depression compared to placebo. 2
- A clinical trial compared women and men suffering PSSD (post-SSRI sexual dysfunction) after 8 weeks of treatment with sertraline, citalopram, or paroxetine. When switched to Trintellix, the PSSD symptoms improved in some trial participants.
- Vortioxetine has a half-life of about 66 hours, which may make gradual withdrawal less troublesome compared to drugs with shorter half-life. Abrupt withdrawal however is associated with adverse effects and should be avoided.
Summary of adverse Trintellix long-term effects:
- Treatment-emergent sexual dysfunction can persist for a long time, even after the drug is withdrawn.
- Suicidality — studies show a slightly protective effect against suicidality in the short-term use of serotonergic medications, however over time this protective effect wanes.9
- Adverse effects such as persisting pulmonary hypertension and withdrawal symptoms in infants born to mothers taking vortioxetine during pregnancy.
- Increased risk of bleeding, i.e., nearly doubled risk of post-partum hemorrhage.
- Weight gain was not reported in short-term use but was reported post-marketing.
- Other post-marketing long-term effects included seizure, rash, and pancreatitis.
- Hyponatremia, especially in elderly patients.7
- Higher risk of upper respiratory tract infection at 48 weeks.2
- Nausea 2X, 3X, 8X that of placebo (dose-dependent) at 48 weeks. 2
- Back pain 4X placebo. (double-blind trial) 2
Short-term adverse effects of Trintellix/vortioxetine:
- Increased risk of suicidality
- Worsening of depression or other symptoms
- Anxiety
- Agitation
- Panic attacks
- Insomnia
- Irritability
- Hostility
- Aggressiveness
- Impulsivity
- Akathisia (psychomotor restlessness) 10
- Serotonin syndrome, caution especially warranted at initiation of Trintellix, or change of dose
- Increased risk of abnormal bleeding
- Mania that lasts at least 1 week.8
- Hypomania (less severe manifestation of mania, lasts 4 days max.)
- Eye issues, i.e., angle closure glaucoma
- Hyponatremia (especially in elderly)
- Nausea, vomiting
- Constipation
Any of the above may persist and become adverse long-term effects of vortioxetine.
