Letters to the Editor
Venlafaxine-Associated Hypomania in Unipolar Depression
Dear Editor:
Antidepressant-induced hypomania and mania have been reported more commonly in cases of bipolar depression than in cases of unipolar depression (1). Tricyclic antidepressants, monoamine oxidase inhibitors, and even selective serotonin reuptake inhibitors have been associated with this switch (1). Newer antidepressants like venlafaxine, which act on multiple specific receptors, have low propensity for the switch (2) but are not completely safe, particularly in patients with bipolar depression or with family history of bipolarity (3–5). The following case report illustrates that venlafaxine may also be associated with a switch to hypomania in unipolar depression.
Case Report
Mr S, aged 26 years and single, presented to our clinic with a 2-year history of sustained sadness of mood, withdrawal, decreased interest in enjoyable activities, increased tiredness, ideas of hopelessness and worthlessness, past attempted suicide, death wish, and decreased sleep and appetite. One year earlier, he had undergone treatment including electro- convulsive therapy (twice) from a private psychiatrist but did not perceive significant benefit. He had been off medication for the 6 months prior to presentation. Two years earlier, his elder brother had committed suicide at age 30 years, following an altercation with family members. Apart from this, there was no personal or family history of affective illness, panic disorder, obsessive–compulsive disorder, substance use, or psychosis. No delusions or hallucinations were forthcoming, either at the time of assessment or historically. Results of a general physical examination and laboratory investigation, including a thyroid function test, were normal. He was diagnosed with severe depression without psychotic symptoms, and treatment with venlafaxine 75 mg daily, together with clonazepam 0.5 mg daily to promote sleep, was started. In the next 3 weeks, he reported 50% improvement in overall symptoms. At the end of week 3, venlafaxine was increased to 112.5 mg daily to enhance his improvement.
At the end of 5 weeks of total treatment, he was noticed to have decreased sleep, over- activity, overtalkativeness, and excessive cheerfulness. He was cracking jokes, voicing grandiose ideas, spending excessively, and smoking more. During interview, he subjectively complained of racing thoughts and new ideas. He himself had discontinued his increased medication after 2 weeks because he felt well. His symptoms continued until his family members brought him to hospital. Drug-induced hypomanic switch was considered, and lithium carbonate was started, along with benzodiazepine. At the end of 4 weeks, he became asymptomatic.
The patient developed possible venlafaxine-induced switch within 8 weeks of starting the medication (6), and the symptoms continued, although they did not worsen, even after he stopped taking the drug. The presence of predisposing factors for bipolarity (7), that is, early age of onset, long duration of a depressive episode, and a family history of suicide, probably made this patient vulnerable to a switch to hypomania on taking therapeutic dosages of venlafaxine, as shown by similar cases in the literature (3). It is important to acknowledge that it is difficult to prove a causal connection between the introduction of venlafaxine and onset of hypomania, but venlafaxine possibly exposed latent bipolarity in this patient, which led to rapid institution of a mood stabilizer to prevent further morbidity.
Prior to starting any antidepressant, clinicians should attempt to obtain risk factors for bipolarity (that is, cyclothymic or hyper- thymic temperament, early onset of depression, acute onset, atypical symptoms, seasonal pattern, and family history of bipolar disorder) to help in early detection and intervention when a manic or hypomanic switch occurs.
References
1. Peet M. Induction of mania with selective serotonin re-uptake inhibitors and tricyclic antidepressants. Br J Psychiatry 1994;164:549–50.
2. Sadock BJ, Sadock V. Comprehensive textbook of psychiatry. 7th ed. Philadelphia: Lippincott Williams and Wilkins; 2000.
3. Shulman RB, Scheftner WA, Nayudu S. Venlafaxine associated mania [letter]. J Clin Psychopharmacol 2001;21:239–41.
4. Stoner SC, Williams RJ, Worrel J, Ramlatchman L. Possible venlafaxine-induced mania [letter]. J Clin Psychopharmacol 1999;19:184–5.
5. Gupta N. Venlafaxine-induced hypomanic switch in bipolar depression. Can J Psychiatry 2001:46:760–1.
6. Altshuler LL, Post RM, Leverich GS, Mikalauskas K, Rosoff A, Ackerman L. Antidepressant-induced mania and cycle alteration: a controversy revisited. Am J Psychiatry 1995;152:1130–8.
7. Akiskal HS, Pinto O. The evolving bipolar spectrum. Psychiatr Clin N Am 1999;22:517–34.
Prabhat K Chand, MD, DNB
Ganjigunte S Kalyani, MBBS
Pratima Murthy, MD
Bangalore, India
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