Comparison of patients experiencing manic switch under antidepressant treatment with patients with major depressive disorder, recurrent type and bipolar affective disorder:neurocognitive functions, quality of life and course of illness after manic switch

Objective: The objective of this study is to compare patients experiencing manic, mixed or hypomanic switch under antidepressant medication (S) with patients with the bipolar affective disorder(BD) and major depressive disorder, recurrent type(unipolar depression=UD) with regard to course of illness, current quality of life and neurocognitive functions. Method:One hundred and thirty three patients with either manic switch (S; n=41), or BD (n=54), or UD (n=38)were included in the study. Switching was defined as manic, mixed and hypomanic symptoms that occurred within the first 6-8 weeks of treatment with an antidepressant medication or the dosage increase. Diagnosis was confirmed withSCID-I interview in all participants. Medical charts and all other related documents of the patients were reviewed for an accurate psychiatric history. The World HealthOrganization Quality of LifeQuestionnaire-ShortForm (WHOQOL-BREF) was usedfor evaluation of quality of life. A Neurocognitive test battery (NT) was used to measure attention, memory and executive functionsin patients were eligible for testing. The socio-demographicand clinical data, WHOQOL-Bref and NTscores were evaluated byANOVA, chi-square, t-test and paired t-test.Regression analysis was performedin order toexcludethe effects ofconfounding factors in the comparison of WHOQOL-Bref and NTscores. Results:In the BD group, the average onset age of the first pyschiatric symptoms (25.15±7.37 years) was lower than both the S group (29.39±10.37 years) and the UDgroup (28.13±7.64 years). However the difference was statistically non-significant(p=0.061). Specific serotonin reuptake inhibitors (SSRIs) were the most frequently used antidepressants followed by the antidepressants with dual neurotransmitter effect in the switchers at the time of the manic switch. Twenty one patients from the S group (48.8%) had spontaneous manic,hypomanic and mixed episodes after switching and the S group also had significantly more frequent mood episodes before switchingcompared to after switching (p=0.009).The BD group had more total number of lifetime mood episodes (7.89±5.33) than both the S (5.54±3.98) and the UD groups (3.13±1.66). The total number of lifetime mood episodes in the S group was significantly higher than that of the than the UD group (p<0.001). The BD (0.79±0.50) and S groups (0.76±0.63) were similar in frequency of lifetime mood episodes whereas the UD patients experienced less frequent mood episodes (0.37±0.26)compared tothe other two groups (p<0.001). The mean total number ofdepressive episodesandthe time spent in depressiveepisodes were significantlylower in the BDgroup compared toboth S and UD groups(p=0.025, p=0.038; p=0.002, p<0.001, respectively). The mean total number ofdepressive episodesand the time spent in depressiveepisodes were similar in S and UD patients.In the BD group the rate of hospitalization (83.3%) was significantly higher than both the S (68.3%) and the UD (36.8%) groups. Similarly,the S group had higher rate of hospitalization than the UD group (p<0.001). The S and BD groups, had similar rates of mood stabilizer and antipsychotic use. In both groups, antidepressant use was limited in contrast to the UD group. Both physical and psychological mean scores of WHOQOL-Bref in the BD group were significantly higherthan the UD group (p=0.007, p<0.001, respectively). The totalnumber of words in categoryfluencytest was significantlyhigher inthe S group (23.58±4.48), compared to that of the BDgroup (19.77±4.33) (p=0.021). Conclusion:Switching to mania/hypomania during the course of an antidepressant treatment seems to be a transition phenomenon between unipolar and bipolar disorders. Based on the clinical features of the switchers, characterized by spontaneous manic/hypomanic recurrences after the first switching despite antibipolar treatment, the course of illness is more likely to be a consequence of a genetic liability rather than being a simple adverse effect of any specific antidepressant medication.Further prospective studies focusing on those UD patients who experience frequent and long lasting depressive episodes may elucidate the clinical features and the pathogenesis of the switching phenomenon. Keywords: Manic switch, unipolar depression, bipolar affective disorder, antidepressants