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Letters   |    
Manic Psychosis After Sertraline and Transcranial Direct-Current Stimulation
Andre Russowsky Brunoni, M.D.; Leandro Valiengo, M.D.; Tamires Zanao; Janaina Farias de Oliveira; Isabela Martins Bensenor, M.D., Ph.D.; Felipe Fregni, M.D., Ph.D.
The Journal of Neuropsychiatry and Clinical Neurosciences 2011;23:E4-E5.
View Author and Article Information

Clinical Research Center, University Hospital, University of São Paulo, Brazil
Dept. of Neurosciences and Behavior, Institute of Psychology, University of São Paulo, Brazil
University of São Paulo,
Medical School, Laboratory of Neuromodulation, Spaulding Rehabilitation Hospital and Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA

Andre Russowsky Brunoni, e-mail: brunoni@usp.br; Felipe Fregni, e-mail: ffregni@bidmc.harvard.edu

To the Editor: There has been a recent renewed interest in testing the technique of transcranial DC stimulation (tDCS) as a potential therapy for major depression. Depending on parameters of stimulation, tDCS can induce significant changes in neuronal spontaneous activity that might be beneficial to modulate mood-associated neural networks. Although tDCS seems to be a relatively safe technique, with a benign profile of adverse effects; there are insufficient safety data, especially in clinical populations, such as in major depression.1 Aiming to provide additional data on potential tDCS adverse effects so as to guide future clinical trials, we report here on a 62-year-old Brazilian woman with DSM-IV–documented psychotic mania after five tDCS sessions.

“Ms. R” presented to our research center to participate in our depression trial2 in May 2010. She was on S-citalopram 20 mg/day for 3 months without improvement; and, at her initial evaluation, she fulfilled eligibility criteria for enrollment, which includes no previous history of bipolar disorder and moderate-to-severe depression (Figure 1). S-citalopram was tapered down during 1 week, and she was then randomized to receive tDCS (2mA/30 minute per day with the anode over the left and cathode over the right dorsolateral prefrontal cortex; current density of 0.06 m2/A) and sertraline 50 mg/day. After 5 days of combined treatment and a weekend interval, she returned agitated and restless. During the interview she was delusional, with auditory hallucinations, claiming that God told her she was protected and could spend any amount of money. Her mood, although excited, quickly swung to hostility and irritability when we explored her delusional content. Her mood scores changed accordingly (Figure 1), with maximum scoring on thought content (delusional), sleep (denying need for sleeping), and elevated mood (euphoric). At that time, we diagnosed her with Bipolar Disorder type I, acute manic episode with psychotic features; she was dropped out of the trial, broke blinding, and started on risperidone 2 mg/day and lithium 900 mg/day. Two weeks later, Ms. R had a serum lithium level of 0.6 meq/liter and presented significant improvement of symptoms (Figure 1).

 
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FIGURE 1.Mood Scores at the Beginning of Treatment (T0), After the 4th Stimulation Sessions (T1), and 2 Weeks After Treatment-Withdrawal and Lithium and Risperidone Introduction (T2)

BDI: Beck Depression Inventory; Ham-D: Hamilton Rating Scale for Depression; MADRS: Montgomery-Asberg Depression Rating Scale; YMRS: Young Manic Rating Scale.

To the best of our knowledge, this is the first report of psychotic mania induced by tDCS. Other reports have described transient hypomania after tDCS, which resolved spontaneously4 or after tDCS withdrawal.5 Along these lines, in a transcranial magnetic stimulation (TMS) review,6 only 13 cases of treatment-emergent mania (TEM) were reported, which was less than 1% of patients stimulated. Most had previous diagnosis of bipolar disorder, and psychotic/delusional symptoms were not reported; in fact, the most similar case to ours was from a 79-year-old woman with recurrent depression who developed mania after 3 days of TMS; however, she was already using tranylcipromine and haloperidol, and had a less severe episode of mania that resolved spontaneously in 2 days. Importantly, in our case, sertraline was combined with tDCS; therefore it is not possible to detangle which intervention (or the combination) was responsible for the symptoms. Also, other interventions could have triggered this episode, although S-citalopram did not induce any adverse effects. Besides these limitations, this report presents valuable safety information and raises important points: 1) combining this report with others, TEM rates with tDCS might be higher than TMS, and perhaps similar than tricyclics (7%–11%)7,8 and selective serotonin reuptake inhibitors (3%–6%);8,2 likewise, tDCS might induce more severe manic episodes than TMS; thus: 2) further tDCS clinical trials for depression should consider protecting patients at high risk of TEM with mood stabilizers9,10 and screening and accessing this risk using appropriate scales.4,11 Future research should attempt to identify whether and which tDCS parameters, such as dosage, electrode positioning, period of treatment, and augmentation with antidepressants are associated with TEM;5 the combination of tDCS and pharmacotherapy should also be carefully investigated.

FF was partially supported by a local grant (FAPESP).

Nitsche  MA;  Boggio  PS;  Fregni  F  et al:  Treatment of depression with transcranial direct current stimulation (tDCS): a review.  Exp Neurol 2009; 219:14–19
[PubMed]
[CrossRef]
 
 Efficacy Study of Transcranial Direct Current Stimulation to Treat Major Depressive Disorder. 2009; from: clinicaltrials.gov.http://clinicaltrials.gov/ct2/show/NCT01033084
 
Hamilton  M:  A rating scale for depression.  J Neurol Neurosurg Psychiatry 1960; 23:56–62
[PubMed]
[CrossRef]
 
Arul-Anandam  AP;  Loo  C;  Mitchell  P:  Induction of hypomanic episode with transcranial direct current stimulation.  J ECT 26:68–69
[PubMed]
[CrossRef]
 
Baccaro  A;  Brunoni  AR;  Bensenor  IM  et al:  Hypomanic episode in unipolar depression during transcranial direct current stimulation Acta Neuropsychiatr (in press)
 
Xia  G;  Gajwani  P;  Muzina  DJ  et al:  Treatment-emergent mania in unipolar and bipolar depression: focus on repetitive transcranial magnetic stimulation.  Int J Neuropsychopharmacol 2008; 11:119–130
[PubMed]
[CrossRef]
 
Nemeroff  CB;  Evans  DL;  Gyulai  L  et al:  Double-blind, placebo-controlled comparison of imipramine and paroxetine in the treatment of bipolar depression.  Am J Psychiatry 2001; 158:906–912
[PubMed]
 
Peet  M:  Induction of mania with selective serotonin re-uptake inhibitors and tricyclic antidepressants.  Br J Psychiatry 1994; 164:549–550
[PubMed]
[CrossRef]
 
Thase  ME:  Bipolar depression: issues in diagnosis and treatment.  Harv Rev Psychiatry 2005; 13:257–271
[PubMed]
[CrossRef]
 
Muzina  DJ;  Calabrese  JR:  Maintenance therapies in bipolar disorder: focus on randomized, controlled trials.  Aust N Z J Psychiatry 2005; 39:652–661
[PubMed]
[CrossRef]
 
Brunoni  AR;  Teng  CT;  Correa  C  et al.  Neuromodulation approaches for the treatment of major depression: challenges and recommendations from a working group meeting.  Arq Neuropsiquiatr 68:433–451
[PubMed]
[CrossRef]
 
References Container

FIGURE 1. Mood Scores at the Beginning of Treatment (T0), After the 4th Stimulation Sessions (T1), and 2 Weeks After Treatment-Withdrawal and Lithium and Risperidone Introduction (T2)

BDI: Beck Depression Inventory; Ham-D: Hamilton Rating Scale for Depression; MADRS: Montgomery-Asberg Depression Rating Scale; YMRS: Young Manic Rating Scale.

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References

Nitsche  MA;  Boggio  PS;  Fregni  F  et al:  Treatment of depression with transcranial direct current stimulation (tDCS): a review.  Exp Neurol 2009; 219:14–19
[PubMed]
[CrossRef]
 
 Efficacy Study of Transcranial Direct Current Stimulation to Treat Major Depressive Disorder. 2009; from: clinicaltrials.gov.http://clinicaltrials.gov/ct2/show/NCT01033084
 
Hamilton  M:  A rating scale for depression.  J Neurol Neurosurg Psychiatry 1960; 23:56–62
[PubMed]
[CrossRef]
 
Arul-Anandam  AP;  Loo  C;  Mitchell  P:  Induction of hypomanic episode with transcranial direct current stimulation.  J ECT 26:68–69
[PubMed]
[CrossRef]
 
Baccaro  A;  Brunoni  AR;  Bensenor  IM  et al:  Hypomanic episode in unipolar depression during transcranial direct current stimulation Acta Neuropsychiatr (in press)
 
Xia  G;  Gajwani  P;  Muzina  DJ  et al:  Treatment-emergent mania in unipolar and bipolar depression: focus on repetitive transcranial magnetic stimulation.  Int J Neuropsychopharmacol 2008; 11:119–130
[PubMed]
[CrossRef]
 
Nemeroff  CB;  Evans  DL;  Gyulai  L  et al:  Double-blind, placebo-controlled comparison of imipramine and paroxetine in the treatment of bipolar depression.  Am J Psychiatry 2001; 158:906–912
[PubMed]
 
Peet  M:  Induction of mania with selective serotonin re-uptake inhibitors and tricyclic antidepressants.  Br J Psychiatry 1994; 164:549–550
[PubMed]
[CrossRef]
 
Thase  ME:  Bipolar depression: issues in diagnosis and treatment.  Harv Rev Psychiatry 2005; 13:257–271
[PubMed]
[CrossRef]
 
Muzina  DJ;  Calabrese  JR:  Maintenance therapies in bipolar disorder: focus on randomized, controlled trials.  Aust N Z J Psychiatry 2005; 39:652–661
[PubMed]
[CrossRef]
 
Brunoni  AR;  Teng  CT;  Correa  C  et al.  Neuromodulation approaches for the treatment of major depression: challenges and recommendations from a working group meeting.  Arq Neuropsiquiatr 68:433–451
[PubMed]
[CrossRef]
 
References Container
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