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Tesi etd-11082018-130850


Thesis type
Tesi di specializzazione (4 anni)
Author
MACCARIELLO, GIUSEPPE
URN
etd-11082018-130850
Title
Predictors of depressive switches in bipolar-I patients treated for mania or mixed-mania with oral antipsychotics and/or mood stabilizers: a prospective observational study
Struttura
MEDICINA CLINICA E SPERIMENTALE
Corso di studi
PSICHIATRIA
Commissione
relatore Prof. Perugi, Giulio
Parole chiave
  • bipolar disorder
  • bipolar depression
  • mania
  • switch
Data inizio appello
11/12/2018;
Consultabilità
parziale
Data di rilascio
11/12/2021
Riassunto analitico
Background: The switch phenomenon is characterized by a sudden transition from a mood episode to another episode of the opposite polarity; this particular feature distinguishes Bipolar Disorder (BD) from all other psychiatric disorders and is related with poor long-term outcome. While switching from depression to mania has been a widely studied issue that originated a great debate in literature in the last 30 years, the switch from mania to depression has been poorly investigated, and only few studies highlighted factors that may be associated with an increased risk of this particular phenomenon. The aim of the present post-hoc analysis was to identify internal and external factors which can predict depressive switches at the final evaluation in a sample of BD-I patients treated for mania or mixed-mania with oral antipsychotics and/or mood stabilizers.
Method: In a multi-centric, prospective, longitudinal, non-interventional study conducted in 34 recruiting Italian centers, 243 BD-I manic patients according to DSM-IV-TR criteria who required to start or switch treatment with oral antipsychotics and/or mood stabilizers were enrolled. Patients underwent a comprehensive 12-week evaluation including the Young Mania Rating Scale (YMRS), the Montgomery and Asberg Depression Rating Scale (MADRS), the Temperament Evaluation of Memphis, Pisa, Paris and San Diego brief-version (briefTEMPS-M), the Childhood Trauma Questionnaire (CTQ) and the Clinical Global Impression Scale-Bipolar Illness (CGI-BP). Switching from mania to depression was defined a posteriori on the basis of a MADRS total score ≥ 15 at week 12. We included also those patients who already had significant depressive symptoms at baseline evaluation (mixed-mania). We used t-test and Chi square-test respectively for comparison of continuous and parametric variables between patients with (DS) and without (NDS) a depressive switch. The relationship between different affective temperaments has been examined and tested with Pearson's correlation coefficients. A stepwise backward logistic regression model was then used to explore the effect of clinical factors on the depressive switch of manic or mixed-manic patients 12 weeks after the initiation or change of treatment with oral antipsychotics and/or mood stabilizers.
Results: Our analyses were performed on the 233 patients who completed the MADRS scale at final evaluation. Among them remission of manic symptoms at week 12 was achieved in 191 patients (82.0%), while a reduction ≥ 50% in YMRS total score from baseline to week 12 was observed in 195 patients (83.7%). As resulted by the MADRS total score ≥ 15 at week 12, only 38 (16.3%) patients showed a depressive switch. Compared to NDS subjects, DS patients had more frequently a history of depressive predominant polarity, higher scores in MADRS and CGI scales at baseline evaluation, higher scores in depressive, cyclothymic and anxious temperamental sub-scales, higher rates of comorbidity with anxiety disorders and were significantly more frequently treated with both FGAs and SGAs. The Pearson's correlations among the briefTEMPS-M temperamental sub-scales showed that cyclothymic, depressive, irritable and anxious temperaments were significantly correlated; on the contrary, hyperthymic temperament scores were not correlated with the other temperamental dimensions, with the exception of irritable temperament. In the logistic regression model, the variables significantly associated with a depressive switch 12 weeks after the initiation or change of therapy for mania or mixed-mania with oral antipsychotics and/or mood stabilizers were the prescription of both FGAs and SGAs, the depressive predominant polarity, the MADRS total score at baseline evaluation, the comorbidity with anxiety disorders and the cyclothymic temperament.
Conclusion: In BD-I patients treated for mania or mixed-mania, 12 weeks after the initiation or change of treatment with oral antipsychotics and/or mood stabilizers, depressive switch has been observed in about 1 out of 6 patients. Several psychopathological and pharmacological variables predicted the switch from mania to depression, such as severity of depressive symptoms at baseline, a course characterized by depressive predominant polarity, anxious comorbidity, cyclothymic temperamental instability and treatment with a combination of both FGAs and SGAs. The presence of these features should be considered for choosing appropriate treatment strategies. In particular, the combination of FGAs and SGAs may be particularly likely to induce depressive switch.  


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