Publication Review: Lithium to prevent Suicide
Increased suicide risk is associated with many psychiatric diagnoses, including major depressive disorder, bipolar disorder, and schizophrenia. Additionally, suicidal risk factors include low social supports, low financial resources, chronic medical conditions, and access to lethal means. Protective factors include religion/spirituality, hobbies, vocation, education, and children/pets. Although advancements in antidepressant medications have generally led to better efficacy and/or decreased side effects, they have done little to address suicide.
Among psychiatric medications, only two (Lithium and Clozapine) have high quality evidence showing reduced suicides. In my experience, Lithium is extremely beneficial for the appropriate patient. I still remember a patient who started seeing me after years of severe depression. At first visit, they appeared despondent and confessed to a daily death wish. After telling me all the medications they had tried and failed, I knew that we needed to give Lithium a chance. The patient was skeptical after being depressed for so long but ultimately agreed. A month later at their follow-up, I began to see improvements. A smile that I hadn’t seen before was now present. They reported better mood, more energy, and less suicidal thoughts. Soon, they began dating, engaging in hobbies, and accomplishing the things they had previously given up hope for. Although I don’t believe in miracle drugs, there was something magical about that patient’s improvements.
Lithium is one of the most well studied medications in psychiatry. Among them, is a landmark publication by Thies-Flechtner et al., 1996 [link to publication]. The authors conducted a randomized prospective study to better understand the effect of Lithium on suicide. The study included 378 patients between 1986 to 1989. These patients had active symptoms of major depressive disorder, bipolar disorder, or schizoaffective disorder. Those with major depression were randomized to either Lithium or an antidepressant called Amitriptyline. Patients with bipolar or schizoaffective disorder were randomized to either Lithium or the mood stabilizer Carbamazepine. The study lasted 2.5 years.
Main Findings- The non-Lithium group had 5 suicide attempts and 9 completed suicides while the Lithium group had 0 attempts and 0 completed suicides. The authors noted that surprisingly, even when patients did not derive the benefit of reduced depression, the Lithium group still exhibited no suicidal behavior. This highlights the possibility that Lithium decreases suicide through a mechanism independent of symptom reduction.
Limitations- While this study was truly groundbreaking, it’s not without limitations. Due to its older publication date, the non-Lithium medications are much less used today. While still helpful, Amitriptyline and Carbamazepine have largely been replaced by newer generation antidepressants (i.e. Prozac, Trintellix) and antipsychotics (i.e. Latuda, Abilify). However, due to the lack of evidence showing decreased suicide rates in newer agents, the superiority of Lithium in preventing suicides likely still holds true.
Summary/Conclusion- Lithium is a medication useful for treating severe major depression and bipolar disorder. This landmark study conducted a randomized trial comparing Lithium to other psychiatric medications for preventing suicide. Out of 378 total patients, the authors found that the Lithium group had 0 suicide attempts and 0 completed suicides, while the comparison group totaled 5 suicide attempts and 9 completed suicides. This study highlights the anti-suicidal properties of Lithium and why it continues to be used by psychiatrists.
