Primary care physicians, nurse practitioners, and other healthcare providers play an important role in the assessment and management of suicide risk. It is estimated that 75% of individuals who die by suicide are in contact with a primary care physician in the year before their death, and nearly half within one month of their death. Only 20% of these patients saw a mental health professional in the preceding month (HHS, 2012, latest available).

Treatment can include medications, addressing substance use disorders, and developing and monitoring a safety plan. Pharmacologic treatment may be helpful in managing underlying mental disorders and the danger of repeated or more dangerous self-directed violence.

All medications (prescription drugs, over-the-counter medications, and supplements) used by patients at risk for suicide should be reviewed. When prescribing drugs to people who are at risk for self-harm, consider the toxicity of prescribed drugs, limit the quantity dispensed or available, and identify another person who is willing to be responsible for securing access to medications (DVA/DOD, 2019).

Proper treatment of depression, bipolar disorder, and borderline personality disorder is essential. This can include selective serotonin uptake inhibitors, serotonin-norepinephrine reuptake inhibitors, tricyclic antidepressants, lithium, or antipsychotics (Harmer et al., 2022). Individuals who have psychiatric and substance use problems should receive psychosocial interventions along with medication.

The only two evidence-based medications that have been shown to lower suicidal behaviors are lithium and clozapine. However, these medications do not reach therapeutic levels immediately. Anxiolytics, sedative/hypnotics, and short-acting antipsychotic medications may be used to directly address agitation, irritability, psychic anxiety, insomnia, and acute psychosis, until such time as a behavioral health assessment can be made. The amount and type of medication must be carefully chosen and titrated when the individual is deemed to be under the influence of alcohol, illicit substances, or other medication in prescribed or overdose amounts.

Lithium

Lithium, which is an effective mood stabilizer, is approved for the treatment of mania and the maintenance treatment of bipolar disorder. Mood stabilizers are used primarily to treat bipolar disorder, mood swings associated with other mental disorders, and, in some cases, to augment the effect of other medications used to treat depression. Several cohort studies have described the anti-suicide benefits of lithium for individuals on long-term maintenance. (NIMH, 2022, June).

A large systematic review sought to determine the efficacy of lithium versus other active treatments or placebo in preventing suicide in patients with unipolar or bipolar mood disorders over a range of 4 to 48 months. Rates of suicide were statistically significantly lower with lithium than with placebo (D’Anci et al., 2019).

The life expectancy of patients with bipolar disorder is reduced by about 10 years compared to the general population and the mortality gap seems to be increasing rather than decreasing over the years. A major cause of death is suicide, which is around 20–30-fold more frequent than in the general population. Around 25–50% of patients with bipolar disorder attempt suicide at some point in their life and around 15% of patients die of suicide. The prevention of suicides is therefore a pivotal goal in the treatment of bipolar disorder (Volkmann et al., 2020).

Lithium has been associated with a reduced suicide risk in patients with affective disorders including bipolar disorder. Long-term studies suggest a strong suicide-preventing effect with suicides being 82% less frequent during lithium treatment. The studies supporting this suicide-preventing effect often include observational data, however, which are prone to bias (Volkmann et al., 2020).

Lithium treatment is likely to be introduced when patients are at their worst, followed by a period of improvement. The increase in suicide risk after discontinuation of lithium treatment may be due to rebound depression or withdrawal effects. Additionally, patients may stop their lithium medication because their health is deteriorating, while continuously adhering to their medication when they are doing well (Volkmann et al., 2020).

Antidepressants

Suicide is strongly associated with poor mental health, especially mood disorders. Antidepressants are the most common treatment for mood disorders, but effective use of these medications requires administration to patients who have been properly diagnosed and then adequately followed up. The importance of improving primary care management of patients experiencing depression cannot be overemphasized.

The use of antidepressants has been shown to reduce the risk of suicide among patients with mood disorders. However, for many years the potential for antidepressants to increase the risk of suicide in certain groups of depressed patients has been debated. Younger patients (< 25 years) who have borderline personality disorder or do not respond to treatment with antidepressants may have an increased potential risk for suicidal ideation, and careful monitoring and close follow-up is necessary when prescribing these drugs (Cato et al., 2019).

Although depressive symptoms are often associated with risk for suicide, no antidepressant medication has yet to be shown to lower suicide risk in depressed patients. However, because of the relationship between low cerebral spinal fluid serotonin levels and the emergence of aggression and impulsivity, the selective serotonin reuptake inhibitors (SSRIs) have been recommended for the treatment of depressive disorders when suicidal risk is present. Treatment with SSRIs must be carefully monitored and managed during the initial treatment phase because of the potential for the possible emergence of suicidal ideation and behaviors during this time. The FDA has recently created a black box warning when prescribing SSRIs for persons under the age of 25.

Antipsychotics

Clozapine

Clozapine (marketed as Clozaril, Fazaclo ODT, Versacloz and generics) is an atypical antipsychotic medicine used to treat schizophrenia in patients whose symptoms are not controlled with standard antipsychotic drugs. Clozapine is also used in patients with recurrent suicidal behavior associated with schizophrenia or schizoaffective disorder (FDA, 2021, November 26).

While clozapine is beneficial for some patients, there are risks associated with this drug. Specifically, clozapine can lead to agranulocytosis, which decreases the number of neutrophils, a type of white blood cell, that function in the body to fight off infections. When neutrophils are significantly decreased, severe neutropenia may result, and the body may become prone to infections. For this reason, patients taking clozapine need to have their absolute neutrophil count (ANC) monitored on a regular basis. This monitoring requirement serves as the basis for the Clozapine Risk Evaluation and Mitigation Strategy (REMS)* (FDA, 2021, November 26).

* The Clozapine REMS Program ensures optimal patient monitoring for and management of clozapine-induced severe neutropenia, providing a centralized system for prescribers and pharmacists in managing patient risk, regardless of which clozapine product is being used.

The REMS program requires frequent visits to healthcare providers for monitoring laboratory results before dispensing medication refills. Because of significant risks associated with clozapine, it is most often used as the antipsychotic of last resort. Repeated blood draws on a weekly basis are inconvenient and may also cause pain and discomfort. Some patients may be unwilling to commit to the level of monitoring and blood draws required for the program. Other significant adverse effects of the medication include weight gain, lipid abnormalities, sialorrhea*, somnolence, and the rarely occurring but serious adverse events of myocarditis and cardiomyopathy (DVA/DOD, 2019).

*Sialorrhea: excessive salivation, drooling.

Long-Acting Injectable Antipsychotics (LAI)

For patients with schizophrenia, findings suggest that LAI use in patients with newly diagnosed schizophrenia is associated with decreased all-cause mortality and suicide risk. Early treatment with LAIs within the first 2 years of oral antipsychotic initiation was associated with a decrease in suicide mortality risk. LAI use in the early stage of treatment should be actively considered for patients with newly diagnosed schizophrenia (Huang et al., 2021).

Antiepileptics

Patients started or who are managed with antiepileptics should be monitored for changes in behavior and the emergence of suicidal thoughts. There is no evidence that antiepileptics are effective in reducing the risk of suicide in patients with a mental disorder (DVA/DOD, 2019).

Antianxiety Agents

Anxiety is a significant and modifiable risk factor for suicide and the use of anti-anxiety agents may have the potential to decrease this risk. Suicidal ideation can be triggered by painful or chronic conditions, anxiety, insomnia, or adverse reactions to medications (Harmer et al., 2022).

Benzodiazepines are indicated for use in patients with sleep disorders, anxiety and affective disorders, delirium, alcohol withdrawal, and aggressive and violent behaviors during psychosis. However, there is a lack of agreement on how sedatives such as benzodiazepine should be used and the role they should play in the treatment of psychiatric disorders (Cato et al., 2019).

Another problem, particularly with regard to the use of benzodiazepines, is that patients may exceed the recommended duration of use. Short-term use (not exceeding 4 weeks) has shown a largely positive risk/benefit ratio, and some studies have shown that benzodiazepine may even have a suicide preventative effect if taken under the right circumstances (Cato et al., 2019).

Benzodiazepines can lower anxiety and reduce insomnia. However, other studies suggest that benzodiazepines are associated with an increased risk of suicidal behavior. Therefore, previous studies have shown mixed results, with symptom relief and a decrease in suicide risk being evident in some cases, but an increase in the risk of suicide in other cases (Cato et al., 2019).

Factors associated with fatal outcomes appear to vary and may be both patient-related and prescriber-related. The impact of benzodiazepines on suicide risk remains uncertain, and further research is required (Cato et al., 2019).