ORIGINAL ARTICLES

EFFICACY OF ARIPIPRAZOLE IN MAJOR DEPRESSIVE EPISODE WITH PSYCHOTIC SYMPTOMS

Simona Trifu1, Stefan Ciurea2
Abstract: Background: This study is a clinical research based on the effectiveness of aripiprazole in major depressive episode . with psychotic symptoms. Material and Methods: 60 patients from Psychiatric Hospital "Prof. Dr. Alexander Obregia ", from 1st of January 2011 to 1st of July 2011, divided into 3 groups of 20 patients diagnosed with major depression with psychotic symptoms. Age range of 38 - 65 years. Regarding sex, prevailed female patients - 49 women (78%) compared to 11 men (22%). Two scales were applied: Hamilton Depression Scale (HAM-D 17), CAQ Multiphasic Personality Questionnaire and Szondi Test. Results: Results were obtained by significant statistically calculations between autoevaluation and heteroevaluation scales scores and taking into account the possibility that the pulsional vector of Szondi Test will be modified in four weeks, in the same decrease direction of depression scales, as well as those aimed at psychotic . aspects Conclusion: Comparing the results obtained from patients before treatment with those obtained one month after treatment there is an improvement in all scores. dministered treatments have resulted improvement of depression and reduction of the clinical factors (D1-D7). Key words: antidepressant, antipsychotic, clinical factors. Rezumat: Introducere: Acest studiu este o cercetare clinic bazat pe eficiena aripiprazolului n episodul depresiv major cu simptome psihotice. Material i metode: 60 de pacien? i de la Spitalul de Psihiatrie "Prof. Dr. Alexandru Obregia", de la 1 ianuarie 2011 pn la inti iulie 2011, mpri? i n 3 grupe de 20 de pacien? i diagnostica? i cu depresie major cu simptome psihotice. Intervalul de vrst este 38 - 65 ani. n ceea ce privete sexul, au predominat pacienii de sex feminin - 49 femei (78%), comparativ cu 11 brbai (22%). Urmatoarele scale au fost aplicate: Scala de Depresie Hamilton (HAM-D 17), chestionarul multifazic de personalitate CAQ i testul Szondi. Rezultate: Rezultatele au fost obinute prin calcule semnificative statistic ntre scorurile scalelor de autoevaluare i heteroevaluare i lund n considerare posibilitatea ca vectorul pulsional de testare Szondi va fi modificat n patru sptmni, n aceeai direcie ca si scala de depresie, precum i aspectele ce vizeaz simptomele psihotice. Concluzie: Comparnd rezultatele obinute de la pacieni nainte de tratament cu cele obinute la o lun dup tratament nu se remarc o mbuntire n toate scorurile; tratamente administrate au avut ca rezultat mbuntirea simptomelor depresive i reducerea factorilor clinici (D1D7). Cuvinte cheie: antidepresive, antipsihotice, factori clinici.

BACKGROUND This study is a clinical research based on the effectiveness of aripiprazole in major depressive episode with psychotic phenomena. Hypothesis from which we started was the superiority of treatment with aripiprazole (associated with the same antidepressant) compared with risperidone and olanzapine (1, 2). There is a difference statistically significant between this three types of medication effects of antipsychotic used to treat major depression with psychotic symptoms. Null hypothesis: There is no statistically significant difference between the effects of three types of medication used to treat major depression with psychotic symptoms (3, 4, 5).

MATERIALS AND METHODS The study was applied on 60 patients hospitalized in the Psychiatric Hospital "Prof. Dr. Alexander Obregia ", from 1st of January 2011 to 1st of July 2011, divided into 3 groups of 20 patients diagnosed with major depression with psychotic symptoms. Age range of 38 - 65 years. Regarding sex, prevailed female patients - 49 women (78%) compared to 11 men (22%). Patients were treated with a combination of antidepressant (same) and antipsychotic. First group was given venlafaxine (AD) and olanzapine (AP) - treatment No.1, the second group was given venlafaxine (AD) and risperidone (AP) - treatment No. 2 and for the third group was prescribed venlafaxine (AD) and aripiprazole (AP) treatment No.3. Patients have been given antipsychotic medication average dose - 10 mg olanzapine, 3 mg risperidone and 10 mg aripiprazole.

Specialist Psychiatrist, MD, PhD, Clinical Hospital of Psychiatry Prof. Dr. Al. Obregia, Berceni Road No. 10-12, Bucharest, Romania. Student, University of Medicine and Pharmacy Carol Davila, Str. Dionisie Lupu No. 34, Bucharest, Romania. Received November 11, 2011, Revised December 20, 2011, Accepted January 13, 2012.

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Simona Trifu, Stefan Ciurea : Efficacy Of Aripiprazole In Major Depressive Episode With Psychotic Symptoms

Initially we wanted a group of women only aged between 18 and 69 years, but 7 patients were excluded due to the significant somatic comorbidity (CICD pathology and thyroid pathology). The first version of this study implies, instead of taking venlafaxine, mirtazapine choosing a combination of SSRIs. For clinical evaluation, two scales were applied: first: Hamilton Depression Scale (HAM-D 17) and the second part (which includes only clinical factors): CAQ Multiphasic Personality Questionnaire and Szondi Test with five applications in order to reveal the pulsional dynamics from latent content (the "migration" of the depression factor, and consequent change of other defense mechanisms used mostly) during treatment. The scales were applied to patients before treatment and one month after its administration. The initial version was for six weeks, but due to a significant improvements in depressive mood and quality of life, the patients did not exceed one month of hospitalization. RESULTS Results were obtained by significant statistically calculations between autoevaluation and heteroevaluation scales scores and taking into account the possibility that the pulsional vector of Szondi Test will be modified in four weeks, in the same decrease direction of depression scales, as well as those aimed at psychotic aspects. For statistical data processing was used SPSS software. Patients were divided into three samples, each sample corresponding to an association of AD and AP. The variables included the results of the Hamilton Test (Ham), D1-D7 clinical factors from CAQ and the pulsional formula from Szondi obtained before (time 1 - M1) and after treatment (time 2 - m2). For this study we compared the results obtained after the medication according to treatment received, then we compared the test results (Ham, D1-D7, Szondi) before and after drug administration for each treatment. Descriptive analysis of variables was performed using nonparametric Smirnov Test - Kolmogorov, trying to observe a normalization of data. Following the descriptive analysis we concluded that due to abnormal distribution for D1 and D5 Ham variables (because p <0.05 => distribution is not normal), data analysis for these variables must be made using nonparametric test Mann Whitney. Regarding the variables D2, D3, D4, D6 and D7 (in this case has been a normal distribution), the analysis is done using T test with Levene test for equality of variance, reaching the inferential data analysis. The analysis was done according to type of treatment given, comparing the results of treatment No. 1 (T1) with the results of treatment No. 2 (T2), T2 results with the results of treatment No. 3 (T3) and results T1 with . T3 (see table no. 1). .One month after admission, after the patients treatment received with AD and AP, applying Hamilton scale scores were observed score ranging between 8 and 11: 8 patients obtained score 8, 17 patients score 9, 31 score 10,4 patients score 11 (see table no. 2). It can be concluded that the medication was effective in 22

relieving depressive mood, while the patients remaining with mild depression.

Sc ore 22 23 24 26 27 28 29 30 31 32 33 T otal

F re que nc y 1 1 1 3 3 6 14 13 12 5 1 60

% 1,7 % 1,7 % 1,7 % 5% 5% 10 % 23,3 % 21,7 % 20 % 8,3 % 1,7 % 100 %

Table 1. Scores of the 60 patients on the Hamilton scale after one month of treatment
Sco re 8 9 10 11 T o tal F re q ue nc y 8 17 31 4 60 % 1 3 ,3 % 2 8 ,3 % 5 1 ,7 % 6 ,7 % 100 %

Table 2. Scores of the 60 patients on the Hamilton scale after one month of treatment DISCUSSIONS Discussion regarding the marginal results of Hamilton Scale : On admission the patient with the highest score of the HAM-D (33) after one month treatment obtained a score of 10 with venlafaxine and olanzapine. Four patients from 5 with a score of 32 on admission obtained a score of 9 to revaluation, 2 of them receiving T1 and 2 of them receiving T2. Following the administration of T1 the fifth patient received 10 on the HAM-D score. Statistical results processing on scales D2, D3, D4, D6 and D7 of the CAQ: Comparing T1 and T2 and using t test for clinical indicators D2, D3, D4, D6, D7 one month after treatment, p values were obtained (D2: p = 0.89> 0.05, D3: p = 0.34> 0.05; D4: p = 0.63> 0.05, D6: p = 0.79> 0.05; D7: p = 0.56> 0.05). The same results were observed for analysis after T2 and T3 (D2: p = 0.10, D3: p = 0.68, D4: p = 0.35; D6: p = 0.60; D7: p = 0.83> 0.05). Analyzing T1 and T3 (D2: p = 0.08, D3: p = 0.26; D4: p = 0.23; D6: p = 0.03; D7: p = 0.28> 0, 05) we observed in D6 indicator, p = 0.03 <0.05. It can be stated so that there is a

Romanian Journal of Psychiatry, vol. XIV, No.1, 2012 difference between T1 and T3 on the indicator D6. Clinical statistical results operationalization on scales D2, D3, D4, D6 and D7 of the CAQ: Antipsychotic treatments associated with venlafaxine: T1 = risperidone T2 = olanzapine T3 = aripiprazole Regarding suicidal depression better results were obtained as follows: aripiprazole> risperidone> olanzapine Regarding depression with agitation: olanzapine> risperidone> aripiprazole Anxious depression: risperidone> olanzapine> aripiprazole Guilt and ressentiment: aripiprazole> olanzapine> risperidone Boredom and withdrawal: aripiprazole> olanzapine> risperidone Clinical scales of the CAQ: D1 = Hypochondriasis D2 = Suicidal Depression D3 = Agitation D4 = Anxious Depression D5 = Depression with low energy D6 = Guilt and ressentiment D7 = Boredom and withdrawal Clinical statistical results operationalization on scales D1 and D5 of the CAQ: Analysing clinical indicators D1, D5 and Hamilton Score by nonparametric Mann Whitney Test. The analysis was made as for other indicators (D2, D3, D4, D6, D7), comparing the T1, T2 and T3 one month after treatment. The results were: Comparing T1 and T2, the values observed are: Ham: p = 0.42, D1: p = 0.52; D5: p = 0.45> 0.05 Comparing T1 and T3, the values observed are: Ham: p = 0.23, D1: p = 0.71; D5: p = 0.53> 0.05 Comparing T2 and T3, the values observed are: Ham: p = 0.62, D1: p = 0.24; D5: p = 0.18> 0.05. Regarding the hypochondriasis scale, the results were: aripiprazole> risperidone> olanzapine Regarding Depression Scale with low energy: aripiprazole> olanzapine> risperidone Regarding total score of Hamilton scale: aripiprazole> risperidone> olanzapine Comparative analysis of Ham scores, D1, D2, D3, D4, D5, D6, D7 - time of admission versus one month of treatment: The results were as follows: For Hamilton scores the improve was major in all treatments with no significant differences from one treatment to another (T1, T2: p = 0.40, T1, T3: p = 2.69, T2, T3: p = 0 18) for the score D1: T1, T2: p = 0.58, T1, T3: p = 0.46, T2, T3: p = 0.88 for D2: T1, T2: p = 0.89, T1, T3: p = 0.83, T2, T3: p = 0.10 for D3: T1, T2: p = 0.34, T1, T3: p = 0.26, T2, T3: p = 0.68 for D4: T1, T2: p = 0.32, T1, T3: p = 0.02, T2, T3: p = 0.35 for D5: T1, T2: p = 0.35, T1, T3: p = 0.50, T2, T3: p = 0.60 for D6: T1, T2: p = 0.24, T1, T3: p = 0.79, T2, T3: p = 0,0,03 for D7: T1, T2: p = 0.56, T1, T3: p = 0.28, T2, T3: p = 0.83 Working hypothesis: We suppose that on deeper level, Szondi Test results level we found higher scores on factors such as Szondi S s, Szondi SCH p, Szondi C d and scores below average on Szondi factor C m and Szondi S h (see table no. 3).
Szondi Factors Individual Average on Factors Mi M= 2,37 M= 2,90 M= 2,68 M= 2,49 M= 2,62 M= 2,81 M= 2,93 M= 2,19 2,64 Global Average FactorsMg The Difference Mg- Mi

Szondi S h Szondi S s Szondi P e Szondi P hy Szondi SCH k Szondi SCH p Szondi C d Szondi C m

-0,27 +0,26 +0,04 -0,15 -0,02 +0,17 +0,29 -0,45

Table 3. Szondi Test results Five Szondi factors are beyond the average population, two of them, Szondi factor P e and Szondi SCH k are slightly exceeding the average, the other three Szondi S s, Szondi SCH p, Szondi C d are above average values. Patients with major depressive episode with psychotic phenomena have attachment problems, feeling the uncertainty of consistent object relations and show enough aggressiveness. To see if the average of these factors differ significantly from the average of other factors considered Szondi was applied Paired Sample T-Test. The working hypothesis of Szondi Test was confirmed: Apparently there is a discrepancy between the results of the clinical scales of CAQ and Szondi Test. This is because this two tools investigate different levels conscious, unconscious of mental functioning. The specifics of these patients diagnosed with major depressive episodes with psychotic phenomena is that they need each other to survive (which no longer remains valid out of the episode). Because of pulsionale pathology (if high scores on suicidal depression) appears an emotional and defensive reorganization using primitive operating mechanisms. We talk about insecure attachment style, with a prevalence of anxious component - avoided. Because of investigation of the patients during the hospitalization, we speak about the prevalence of attachment style that suggests a child specific attachment. 23

Simona Trifu, Stefan Ciurea : Efficacy Of Aripiprazole In Major Depressive Episode With Psychotic Symptoms

CONCLUSIONS Comparing the results obtained from patients before treatment with those obtained one month after treatment there is an improvement in all scores. Administered treatments have resulted improvement of depression and reduction of the clinical factors (D1-D7). In Ham scores, D1, D2, D3, D5, D6 and D7 it does not observe significant statistically differences between risperidone and olanzapine treatment results, but specifying when revaluation improve scores for both types of medication. However there are statistically significant differences in terms of differential analysis aripiprazole versus olanzapine versus risperidone, aripiprazole size: hypochondriasis, depression, suicidal thoughts, anxiety, depression with low energy, guilt and ressentiment, boredom and social withdrawal. Especially, the biggest statistically significant difference is for D4 clinical factor, anxious depression, comparing T1 and T2 or T1 and T3 is not any difference, but there is a statistical difference when comparing T2 to T3. It can be said that the effect of the third treatment (venlafaxine + aripiprazole) was better in size D4. It has been observed a complete remission of DM post-treatment (HAM-D 17 score 8 and the lack of criteria DSM-IV) of 8 patients and a favorable response in 80% of patients (HAM-D score 10). The remaining 4 patients (6.7%) obtained 11 score on HAM-D 17 revaluation, while remaining a slight depression. 87% of patients experienced a significant improvement of hypochondriasis (D1 score 14). For suicidal depression, symptoms were improved to 85% of patients. Agitation was remitted in 93% of patients. 97% from 60 patients studied, anxious depression scale evaluation of CAQ, after treatment, showed a decrease in symptoms, but favoring the group receiving the treatment No. 3. Effects of medication on patients' low energy (D5) were not very well defined, 50% of patients still accusing a state of fatigue and low energy. Feelings of guilt (D6) posttreatment were reduced to 76.6% for the patients. For boredom and withdrawal (D7), 36% of patients still complain feelings of depression and believes that interaction with other people is useless. Weight gain was observed in 40% of patients based on the response given to the Hamilton evaluation questionnaire and based on clinical findings. A percentage of 35% of patients who received venlafaxine and risperidone and 48% of those who were administered venlafaxine and olanzapine had

nausea, while only 20% of patients who received venlafaxine and aripiprazole presented these accusations. On the group receiving treatment with venlafaxine and aripiprazole, nausea occurred in fewer patients than other groups. Professional activity has not undergone major changes depending on treatment. Only 15% of patients, divided in the 3 groups, complaints lack of interest on work or hobbies. The remaining patients have their work and leisure activities resumed. Patients who on the first review reported onset insomnia, on the second evaluation they responded positively to treatment indicating deep sleep. All three treatments proved to be effective in relieving insomnia without clear differentiation could be observed between them. Individually, each of the 60 patients showed a general improvement in symptoms and an improvement in psychotic major depression. Major changes occurred on score of HAM-D 17 and in relieving symptoms of anxiety and insomnia on treatment with venlafaxine and aripiprazole. Limitations of the study: -Small number of patients (60 cases) -Insufficient time monitoring for one month, we suggest that most patients to be re-evaluated from month to month -Insufficient time monitoring for other clinical issues (change in appetite, body weight, lipid parameters) -Insufficient time to investigate operating pulsional unconsciously and level of conversion of defense mechanisms (4 weeks is not enough to change the Szondi pulsional formula) -Perceptions of the clinical authors in previous integrating individual experience is already made on the efficacy of aripiprazole in major depressive episode, regarding depression scales in anhedonia. REFERENCES
1.Sandson NB, Armstrong SC, Cozza KL. An Overview of Psychotropic Drug. Drug Interactions Psychosomatics 2005;46: 464-494. 2.2. Sharif Z. Side Effects as Influencers of Treatment Outcome. J Clin Psychiatry 2008; 69(3): 38-43. 3.Preskorn SH, Flockhart D. 2010 Guide to Psychiatric Drug Interactions. Primary Psychiatry 2009;16(12): 45-74. 4.Bazire S. Psychotropic Drug Directory. Tarxiene, Malta: Gutenberg Press Limited, 2009. Sharif ZA. Pharmacokinetics, Metabolism and Drug- Drug Interactions of Atypical Antipsychotics in Special Populations. J Clin Psychiatry 2003; 5(6): 22-25.

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