Antipsychotic use has expanded significantly into the treatment of mood disorders, with second-generation agents now being widely used for conditions such as bipolar disorder and major depressive disorder. As antipsychotic exposure increases, so does the incidence of tardive dyskinesia (TD). This discussion highlights the similarities and differences in TD risk factors, presentation, and impact between patients with schizophrenia and those with primary mood disorders.

Back when only first-generation antipsychotics were available, people with mood disorders were at a higher risk of developing TD, potentially due to overtreatment with postsynaptic dopamine antagonists. People who do not have schizophrenia may be more sensitive to postsynaptic dopamine antagonism and therefore potentially more likely to develop akathisia, parkinsonism, and dystonia—all known risk factors for TD.

With second-generation antipsychotics, we find ourselves in an interesting situation, as antipsychotic use has expanded significantly into the realm of mood disorders, much more so than with first-generation agents. Patients on second-generation antipsychotics are generally receiving lower doses, which may reduce their risk of neuromotor side effects. However, with more people being exposed to these medications, we are now seeing nearly equal numbers of TD cases among both patients with schizophrenia and those with mood disorders.

Currently, schizophrenia and psychotic disorders rely on postsynaptic dopamine-blocking agents as a mainstay of treatment, although future presynaptic modulators may reduce their need and the risk of TD. In major depressive disorder, since second-generation antipsychotics are a US Food and Drug Administration (FDA)–approved augmentation treatment, they are still used a lot, and it can sometimes be difficult to discontinue their use. And even when antipsychotics are stopped, TD may persist, so both patients with schizophrenia and patients with mood disorders can benefit from FDA-approved VMAT2 inhibitors.

Individuals with mood disorders are often very aware of their TD-associated movements because they are typically more socially active than those with schizophrenia, so others may point the movements out to them. This awareness, however, can lead to secondary depression or social withdrawal if they feel stigmatized. In contrast, some patients with schizophrenia may not notice their TD movements as much, or they might be less socially engaged, which can cause a delay in seeking help.

When I first started my training, we only had first-generation antipsychotics, and I used to say that one had to really “earn” their antipsychotic by having schizophrenia. A paradigm shift occurred with second-generation antipsychotics when we learned that they could be very effective for mood disorders. We have greatly expanded their use, not only in terms of indications but also across a wider range of age groups, including both younger and older patients. However, advanced age is an important risk factor for TD. So, despite the overall lower risk from second-generation antipsychotics, their increased use may be fueling an unnoticed epidemic.

Many of these medications are foundational in the treatment of patients, especially those with schizophrenia, so decreasing dosages or discontinuing treatment is not always an option. There may be situations in which a patient’s medication regimen is literally lifesaving for them, so it is very risky to destabilize them by altering their therapeutic regimen. The sooner you or your patient can recognize TD and have a discussion about initiating definitive treatment with VMAT2 inhibitors, the better.

What fascinates me about TD is its lack of a sensory component. In fact, patients often do not feel it, but they may feel secondary complications such as mouth sores. This can delay recognition, especially in patients with schizophrenia, who may be less aware of or eager to seek treatment. It is crucial to remember that even mild movements can be distressing for an individual patient, and we should not assume that the patient is not bothered by them or that they do not need treatment just because their movements are not severe. It is important not to make treatment-related decisions for a patient; it is really a collaborative decision.

Psychiatry has had a very interesting and tumultuous relationship with TD. We started by fearing it, moved to ignoring it, and finally appreciated that TD is both real and common. We have embraced it as one of our own disorders, not something that we need to dump on another specialty. Personally, however, I have been more interested in the experiences of people living with TD than in the condition itself, and my research has been eye-opening.

In 2023, I led the publication of a large survey of patients with TD who were diagnosed with schizophrenia, bipolar disorder, or major depressive disorder. We found that the similarities in the impact of TD far outweighed the differences between these underlying conditions. Interestingly, many patients reported experiencing significant functional difficulties, such as falling asleep. I have to admit that I had never thought to ask a patient if their TD was affecting their ability to fall sleep. This may help explain why so many patients with TD are prescribed medications such as benztropine or benzodiazepines, or why some individuals may have more frequent alcohol use. But the take-home message was that no matter who develops TD, its impact is profound.

The changes in the world of TD have been significant, and we are now beginning to bravely confront TD by identifying it appropriately, rather than looking the other way, and, if there is impairment, treating it just as the American Psychiatric Association (APA) criteria advise. We are fortunate to have treatment options.