The weight loss drug with the most prominent suicide-related warning is Contrave (naltrexone/bupropion), which carries an FDA boxed warning, the agency’s most serious safety label, for suicidal thoughts and behaviors. A second medication, Qsymia (phentermine/topiramate), also has documented links to depression and suicidal ideation. And a third drug, rimonabant, was pulled from the global market entirely over psychiatric risks including suicidality. The newer GLP-1 drugs like Ozempic and Wegovy have drawn headlines on this topic, but regulators have not found evidence connecting them to suicide risk so far.
Contrave: The Only Active Drug With a Boxed Warning
Contrave combines two older medications: naltrexone, used for addiction treatment, and bupropion, an antidepressant. Because bupropion belongs to the antidepressant class, Contrave inherits the FDA’s strongest possible warning. The boxed warning states that antidepressants increased the risk of suicidal thoughts and behavior in children, adolescents, and young adults in short-term trials. Contrave is not approved for treating depression or any other psychiatric disorder, but because it contains an antidepressant ingredient, the warning applies.
The risk is not uniform across age groups. Clinical trials showed no increase in suicidal thoughts or behavior in adults over 24, and people aged 65 and older actually had a reduced risk. The concern is concentrated in younger patients, which is why the warning specifically flags children, adolescents, and young adults. If you have a history of depression, bipolar disorder, or suicidal thoughts, this medication warrants a careful conversation with your prescriber about whether the benefits outweigh the risks.
Qsymia: Depression and Suicidal Ideation in Trials
Qsymia pairs phentermine (a stimulant appetite suppressant) with topiramate, a drug originally developed for epilepsy and migraines. Topiramate is the component tied to mood-related side effects. In one-year controlled trials of the higher dose, 7.6% of adults reported depression or mood problems, compared to 3.4% on placebo. At the lower dose, the rate was 3.8%, barely above placebo.
The signal was sharper in younger patients. In a clinical trial of adolescents aged 12 and older, one out of 167 patients on Qsymia (0.6%) experienced suicidal ideation and behavior severe enough to require hospitalization. No patients in the placebo group reported suicidal thoughts or behavior. Depression was also more common in the adolescent group: 4% on the higher dose versus 0% on placebo.
These numbers are small in absolute terms, but they were significant enough for the FDA to include mood-related warnings on the label. People with a history of depression should be aware that topiramate-containing medications can worsen mood symptoms, and stopping the drug abruptly rather than tapering can also trigger problems.
Rimonabant: Withdrawn Over Psychiatric Harm
The most dramatic case of a weight loss drug linked to suicide is rimonabant, sold in Europe under the brand name Acomplia. Rimonabant worked by blocking receptors in the brain’s endocannabinoid system, essentially the opposite of how cannabis stimulates appetite. It was effective for weight loss, but it also interfered with mood regulation in ways that proved dangerous.
The FDA never approved rimonabant for the U.S. market. An advisory committee voted unanimously against it, citing the risk of psychiatric adverse events with particular emphasis on suicidality. The European Medicines Agency had approved it in 2006 but reversed course in January 2009, ordering the drug withdrawn.
A closer look at the data, reviewed years later, reveals a complicated picture. Across 13 pooled clinical trials involving 14,832 patients, no completed suicides were recorded during the main study period. Two suicides were later referenced by the FDA: one in a patient taking a low dose of rimonabant whose death was subsequently reclassified after independent review as lacking enough information to confirm it was a suicide, and one in a heart disease study. Post-marketing data covering 78,610 patients in countries where the drug was sold contained no references to completed suicides either. The psychiatric concern was driven more by rates of depression, anxiety, and suicidal ideation than by completed suicides. Regardless, the risk was deemed unacceptable, and the entire class of drugs targeting that brain receptor was abandoned.
GLP-1 Drugs: Headlines but No Confirmed Link
Semaglutide (Ozempic, Wegovy) and tirzepatide (Mounjaro, Zepbound) have received enormous attention for both their effectiveness and their potential risks. Reports of suicidal thoughts in people taking these drugs surfaced in adverse event databases, prompting the FDA and European regulators to launch formal investigations.
The FDA’s preliminary evaluation did not find evidence that GLP-1 drugs cause suicidal thoughts or actions. Reviews of clinical trials, large outcome studies, and observational studies found no association. The agency noted that adverse event reports were often limited in detail and that the events could be influenced by other factors, making it impossible to draw a clear line between the medication and the reported thoughts.
That said, the FDA has not fully closed the book. Because the number of suicidal events in both the drug groups and placebo groups was small, regulators stated they cannot definitively rule out that a small risk exists. The investigation is ongoing. For now, these drugs do not carry any suicide-related warning on their labels, which distinguishes them clearly from Contrave and Qsymia.
Why Psychiatric History Matters
Clinical trials for weight loss medications routinely exclude people with significant mental health conditions, including depression, suicidality, schizophrenia, bipolar disorder, eating disorders, substance use disorder, and ADHD. This means the safety data collected during trials may not fully reflect what happens when these drugs are prescribed in the real world to people managing psychiatric conditions alongside obesity.
This gap matters because obesity itself is associated with higher rates of depression and anxiety. Many people seeking weight loss treatment already live with mood disorders. If you have a psychiatric history, the choice of weight loss medication becomes a balancing act. Contrave’s boxed warning makes it the most scrutinized option in this context, but Qsymia’s topiramate component also deserves attention. GLP-1 drugs currently appear to carry no established psychiatric risk, though the investigation continues.
Warning Signs to Watch For
Regardless of which weight loss medication you take, new or worsening mood changes in the first weeks and months deserve attention. The patterns to watch for include persistent sadness or hopelessness that feels different from your baseline, withdrawing from friends and activities, increased irritability or agitation, sleep changes that don’t have an obvious explanation, and thoughts about self-harm or suicide. These can emerge gradually, which is why people close to you may notice changes before you do.
The risk window is typically highest early in treatment and during dose changes. If you notice mood shifts after starting a new weight loss drug or moving to a higher dose, that timing is not a coincidence and is worth reporting to your prescriber promptly.