From the Guidelines
Antidepressants that can potentially trigger mania include selective serotonin reuptake inhibitors (SSRIs) like fluoxetine (Prozac), sertraline (Zoloft), and escitalopram (Lexapro), as well as serotonin-norepinephrine reuptake inhibitors (SNRIs) such as venlafaxine (Effexor) and duloxetine (Cymbalta). Bupropion (Wellbutrin) and tricyclic antidepressants like amitriptyline can also cause this reaction, as noted in the study by 1. This risk is particularly high in patients with bipolar disorder who are not on mood stabilizers. The switch to mania typically occurs within the first few months of treatment and presents as elevated mood, decreased need for sleep, racing thoughts, increased energy, impulsivity, and sometimes psychotic symptoms. The biological mechanism involves excessive stimulation of serotonergic and noradrenergic pathways in vulnerable individuals, as discussed in 1. If mania develops, the antidepressant should be discontinued immediately and a mood stabilizer or antipsychotic medication should be started, as recommended in 1 and 1. Patients with a personal or family history of bipolar disorder should be closely monitored when starting antidepressant therapy, and clinicians should consider prescribing a mood stabilizer concurrently to prevent this potentially dangerous side effect. Some key points to consider when prescribing antidepressants to patients at risk of mania include:
- Close monitoring for signs of mania, such as elevated mood, decreased need for sleep, and increased energy
- Starting with a low dose and gradually increasing as needed
- Using a mood stabilizer concurrently to prevent mania
- Avoiding the use of antidepressants in patients with a history of mania or bipolar disorder, unless absolutely necessary and with close monitoring. It's also important to note that the study by 1 highlights the importance of slow up-titration and close monitoring when starting antidepressant therapy, particularly in younger children. Additionally, the study by 1 recommends the use of lithium or valproate for the maintenance treatment of bipolar disorder, and the use of antidepressant medicines in combination with a mood stabilizer for the treatment of moderate or severe depressive episodes of bipolar disorder. The study by 1 also discusses the efficacy of anticonvulsants, such as valproate and carbamazepine, for the treatment of bipolar disorder in youths. Overall, the key to preventing mania in patients taking antidepressants is close monitoring and careful consideration of the patient's individual risk factors and medical history.
From the FDA Drug Label
Among 633 adult patients who overdosed on fluoxetine hydrochloride alone, 34 resulted in a fatal outcome, 378 completely recovered, and 15 patients experienced sequelae after overdosage, including abnormal accommodation, abnormal gait, confusion, unresponsiveness, nervousness, pulmonary dysfunction, vertigo, tremor, elevated blood pressure, impotence, movement disorder, and hypomania Other important adverse events reported with fluoxetine overdose (single or multiple drugs) include coma, delirium, ECG abnormalities (such as QT interval prolongation and ventricular tachycardia, including torsades de pointes–type arrhythmias), hypotension, mania, neuroleptic malignant syndrome–like events, pyrexia, stupor, and syncope
The antidepressant fluoxetine can prompt mania or hypomania 2.
- Mania and hypomania are listed as potential sequelae of overdose.
- These conditions are indicative of the drug's potential to induce manic episodes.
From the Research
Antidepressants that can Prompt Mania
- Antidepressants are not recommended as monotherapy for bipolar disorder, as they can prompt mania 3
- Traditional antidepressants, such as selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs), can increase the risk of manic episodes in patients with bipolar disorder 4, 5
- The use of antidepressants in bipolar depression is controversial due to limited efficacy evidence and the concern for potential harm, including the risk of prompting mania 5
Examples of Antidepressants that can Prompt Mania
- SSRIs, such as fluvoxamine, fluoxetine, sertraline, paroxetine, and escitalopram 6
- SNRIs, such as venlafaxine and duloxetine 6
- Other antidepressants, such as mirtazapine and bupropion, which can be used in combination with mood stabilizers or atypical antipsychotics 7