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Letters   |    
Hypomania as a Genuine Side Effect of Fluoxetine
Ashish Aggarwal, M.D.; Dinesh Dutt Sharma, M.D.; Ravi Chand Sharma, M.D.; Ramesh Kumar, M.D.
The Journal of Neuropsychiatry and Clinical Neurosciences 2011;23:E23-E24.

To the Editor: Antidepressant-induced manic switch is generally seen in patients with risk factors for bipolar disorder. To the contrary, the authors hereby report a case of an adolescent boy who developed fluoxetine-induced hypomania but did not have any risk factor for bipolarity. Hypomania might be a genuine side effect associated with antidepressants like fluoxetine

Literature suggests that antidepressants can precipitate mania in patients with unipolar/bipolar disorder.1 During the pre-drug era, spontaneous mild depression after a manic episode and spontaneous hypomania after a melancholic episode were common, and had no bearing on the primary diagnosis.2 Previous reports of fluoxetine-induced mania/hypomania have been mostly in patients with depression.3,4 It can be argued that these cases had natural manic episodes of bipolar disorder. On the contrary, fluoxetine has been argued to be useful in bipolar II disorder.5 We hereby report a case of an adolescent boy who developed hypomania while on fluoxetine without any risk factor for manic switch.

A 17-year-old boy was suffering from tension-type headache along with mild episodic anxiety symptoms. His past, family, and personal history were nonsignificant. There was no history to suggest depressive features. He was started on fluoxetine 20 mg per day along with relaxation exercises. The patient followed up after a period of 3 weeks with complaints of decreased need for sleep, talkativeness, over-familiarity, increased activity levels, and demanding behavior for the past 4 days. On examination, he had increased psychomotor activity, euphoric affect, racing thoughts, grandiose ideas, and inflated self-esteem. No other significant history was elicited. All his biochemical parameters, including CT head scan, were normal. Diagnosis of fluoxetine-induced hypomania was made. Fluoxetine was stopped, and clonazepam 1 mg was started. The patient improved in hypomanic symptoms in a week's time. He was then followed up, and he continued reporting headache. Amitriptyline was started, gradually increased to 25 mg per day. The patient has been maintained on this dose for the last 8 months without any recurrence of hypomania.

Previous reports of hypomania/mania on fluoxetine have been in cases with a diagnosis of depressive disorder or those with risk factors for bipolar disorder.3,4,6,7 Ours was a case of tension-type headache with nonspecific anxiety symptoms, and did not have any features of depression or any risk factors for bipolar disorder.

We could find only few case reports of mania being induced by SSRIs in patients with obsessive-compulsive disorder (OCD) with or without mood disorder.8,9 OCD is also commonly associated with depressive disorder, and recent literature has pointed toward comorbidity of OCD with bipolar disorder.10,11

Probability of mania or hypomania later was remote in this case because of the absence of various risk factors for bipolar disorder.12,13 The absence of depressive disorder or family history of bipolar disorder, temporal correlation between fluoxetine therapy and onset of hypomania, and quick recovery with a low dose of benzodiazepine after complete withdrawal of fluoxetine shows that this is a case of true fluoxetine-induced hypomania.

Unique points of our case are the facts that the patient did not have any depressive disorder or risk factor for mania and the fact that the patient had been well-maintained on amitriptyline. Previous reports have suggested that tricyclic antidepressants like amitriptyline are more commonly associated with manic switch than are SSRIs.14 The biological mechanism of SSRI-induced mania remains unclear, although serotonergic and catecholamine mechanisms have been implicated.15

Tension-type headache is not even a probable risk factor for antidepressant-induced mania or hypomania. It can be argued confidently that previous case reports may have been having natural bipolar disorder and in other cases, probability of mania or hypomania in future cannot be ruled out.

Our case thus represents genuine fluoxetine-induced hypomania. More such reports would help us to differentiate the drug-induced mania or hypomania from a natural switch.

Howland  RH:  Induction of mania with serotonin reuptake inhibitors.  J Clin Psychopharmacol 1996; 16:425–427
[PubMed]
[CrossRef]
 
Angst  J;  Sellaro  R:  Historical perspective and natural history of bipolar disorder.  Biol Psychiatry 2000; 48:445–457
[PubMed]
[CrossRef]
 
Lebegue  B:  Mania precipitated by fluoxetine.  Am J Psychiatry 1987; 144:1620
[PubMed]
 
Venkataraman  S;  Naylor  MW;  King  CA:  Mania associated with fluoxetine treatment in adolescents.  J Am Acad Child Adolesc Psychiatry 1992; 31:276–281
[PubMed]
[CrossRef]
 
Amsterdam  JD;  Shults  J:  Fluoxetine monotherapy of bipolar type II and bipolar NOS major depression: a double-blind, placebo-substitution, continuation study.  Int Clin Psychopharmacol 2005; 20:257–264
[PubMed]
[CrossRef]
 
Chouinard  G;  Steiner  W:  A case of mania induced by high-dose fluoxetine treatment (letter).  Am J Psychiatry 1986; 143:686
[PubMed]
 
Damodaran  SS;  Khanna  R:  Fluoxetine-induced mania in an adolescent: possible implications (letter).  Indian J Psychiatry 1992; 34:395–396
[PubMed]
 
Go  FS;  Malley  EE;  Birmaher  B  et al:  Manic behaviors associated with fluoxetine in three 12- to 18-year-olds with obsessive-compulsive disorder.  J Child Adolesc Psychopharmacol 1998; 8:73–80
[PubMed]
[CrossRef]
 
Diler  RS;  Avei  A:  SSRI-induced mania in obsessive-compulsive disorder (letter).  J Am Acad Child Adolesc Psychiatry 1999; 38:6–7
[PubMed]
[CrossRef]
 
Zutshi  A;  Kamath  P;  Reddy  YC:  Bipolar and nonbipolar obsessive-compulsive disorder: a clinical exploration.  Compr Psychiatry 2007; 48:245–251
[PubMed]
[CrossRef]
 
Angst  J;  Gamma  A;  Endrass  J  et al:  Obsessive-compulsive syndromes and disorders: significance of comorbidity with bipolar and anxiety syndromes.  Eur Arch Psychiatry Clin Neurosci 2005; 255:65–71
[PubMed]
[CrossRef]
 
Holma  KM;  Melartin  TK;  Holma  IA  et al:  Predictors for switch from unipolar major depressive disorder to bipolar disorder type I or II: a 5-year prospective study.  J Clin Psychiatry 2008; 69:1267–1275
[PubMed]
[CrossRef]
 
Henry  C;  Sorbara  F;  Lacoste  J  et al:  Antidepressant-induced mania in bipolar patients: identification of risk factors.  J Clin Psychiatry 2001; 62:249–255
[PubMed]
[CrossRef]
 
Peet  M:  Induction of mania with selective serotonin re-uptake inhibitors and tricyclic antidepressants.  Br J Psychiatry 1994; 164:549–550
[PubMed]
[CrossRef]
 
Howland  RH:  Induction of mania with serotonin reuptake inhibitors.  J Clin Psychopharmacol 1996; 16:425–427
[PubMed]
[CrossRef]
 
References Container
+

References

Howland  RH:  Induction of mania with serotonin reuptake inhibitors.  J Clin Psychopharmacol 1996; 16:425–427
[PubMed]
[CrossRef]
 
Angst  J;  Sellaro  R:  Historical perspective and natural history of bipolar disorder.  Biol Psychiatry 2000; 48:445–457
[PubMed]
[CrossRef]
 
Lebegue  B:  Mania precipitated by fluoxetine.  Am J Psychiatry 1987; 144:1620
[PubMed]
 
Venkataraman  S;  Naylor  MW;  King  CA:  Mania associated with fluoxetine treatment in adolescents.  J Am Acad Child Adolesc Psychiatry 1992; 31:276–281
[PubMed]
[CrossRef]
 
Amsterdam  JD;  Shults  J:  Fluoxetine monotherapy of bipolar type II and bipolar NOS major depression: a double-blind, placebo-substitution, continuation study.  Int Clin Psychopharmacol 2005; 20:257–264
[PubMed]
[CrossRef]
 
Chouinard  G;  Steiner  W:  A case of mania induced by high-dose fluoxetine treatment (letter).  Am J Psychiatry 1986; 143:686
[PubMed]
 
Damodaran  SS;  Khanna  R:  Fluoxetine-induced mania in an adolescent: possible implications (letter).  Indian J Psychiatry 1992; 34:395–396
[PubMed]
 
Go  FS;  Malley  EE;  Birmaher  B  et al:  Manic behaviors associated with fluoxetine in three 12- to 18-year-olds with obsessive-compulsive disorder.  J Child Adolesc Psychopharmacol 1998; 8:73–80
[PubMed]
[CrossRef]
 
Diler  RS;  Avei  A:  SSRI-induced mania in obsessive-compulsive disorder (letter).  J Am Acad Child Adolesc Psychiatry 1999; 38:6–7
[PubMed]
[CrossRef]
 
Zutshi  A;  Kamath  P;  Reddy  YC:  Bipolar and nonbipolar obsessive-compulsive disorder: a clinical exploration.  Compr Psychiatry 2007; 48:245–251
[PubMed]
[CrossRef]
 
Angst  J;  Gamma  A;  Endrass  J  et al:  Obsessive-compulsive syndromes and disorders: significance of comorbidity with bipolar and anxiety syndromes.  Eur Arch Psychiatry Clin Neurosci 2005; 255:65–71
[PubMed]
[CrossRef]
 
Holma  KM;  Melartin  TK;  Holma  IA  et al:  Predictors for switch from unipolar major depressive disorder to bipolar disorder type I or II: a 5-year prospective study.  J Clin Psychiatry 2008; 69:1267–1275
[PubMed]
[CrossRef]
 
Henry  C;  Sorbara  F;  Lacoste  J  et al:  Antidepressant-induced mania in bipolar patients: identification of risk factors.  J Clin Psychiatry 2001; 62:249–255
[PubMed]
[CrossRef]
 
Peet  M:  Induction of mania with selective serotonin re-uptake inhibitors and tricyclic antidepressants.  Br J Psychiatry 1994; 164:549–550
[PubMed]
[CrossRef]
 
Howland  RH:  Induction of mania with serotonin reuptake inhibitors.  J Clin Psychopharmacol 1996; 16:425–427
[PubMed]
[CrossRef]
 
References Container
+
+

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