Comparison of Different Antidepressants and Psychotherapy in the Short-term Treatment of Depression

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1 ORIGINAL COMPARISON PAPER OF DIFFERENT ANTIDEPRESSANTS AND PSYCHOTHERAPY IN THE SHORT-TERM TREATMENT OF DEPRESSION Comparison of Different Antidepressants and Psychotherapy in the Short-term Treatment of Depression Azhar MZ, Noorjan KON, Zubaidah JO Department of Psychiatry, Faculty of Medicine & Health Sciences, Universiti Putra Malaysia. This paper reports the result of an analysis of data of brief therapy for patients with depression referred by physicians in a busy specialist hospital in Kuala Lumpur. The patients were divided into three groups at random using one of three antidepressants i.e. escitalopram, sertraline, or fluoxetine. All patients received cognitive behavior therapy. The therapy was aimed for a maximum of twelve sessions after which the patients will be discharged. However there were patients on escitalopram and sertraline that went on follow-up sessions monthly till six months and these patients were analized separately. There were 32 patients in the escitalopram group, 33 patients in the sertraline group, and 31 patients in the fluoxetine group. The result shows that all the groups were similar in the severity and scores pre-treatment but post-treatment there were a significant difference among them. All groups showed significant improvements in all modalities of measurements. However the escitalopram group showed better improvement compared to the two other groups. Key words: Depression, antidepressants, cognitive behaviour therapy, psychotherapy Malaysian Journal of Psychiatry September 2007, Vol. 16, No. 2 Introduction Antidepressants have been used for many years to treat depression with significant success. The most used group of antidepressants is the specific serotonin reuptake inhibitor (SSRI). All the three drugs used in this study i.e. escitalopram (ESC), sertraline (STR), and fluoxetine (FXT) are SSRIs. They have all been shown to be very effective in the treatment of major depressive disorders with ESC being the youngest of the three to be used in Malaysia. Cognitive behaviour therapy has also been shown to be successful at treating major depressive disorder especially in the last few years where the technique and theory have been refined (1). It has also been demonstrated to be very successful in Malaysian patients (2). In this study we try to show how effective is the treatment when given in combination with SSRI and which SSRI does better in this combination. As far as we know, there has been no such Correspondence Dr. Azhar M. Zain, Professor, Dept. of Psychiatry, Faculty of Medicine & Health Sciences, Universiti Putra Malaysia, UPM, Serdang. study in Malaysia to show the comparison of pharmacotherapy and psychotherapy for depression where the psychotherapy is the permanent treatment. This is certainly the first study of its kind in this part of the world. Methodology Sample Subjects selected for the study consisted of male and female patients diagnosed with major depression by a psychiatrist based on DSM IV (3) criteria. The subjects were recruited from among the patients referred by physicians to the psychiatry and psychotherapy clinic of a specialist hospital in Kuala Lumpur. They were then divided at random into three groups, i.e. (1) the escitalopram group (ESC), (2) the sertraline group (STR) and (3) the fluoxetine group (FXT). All groups received cognitive behavior therapy (CBT) as standard treatment. The treatment was carried out over a period of twelve weeks for patients in the FXT group and twelve weeks plus three monthly booster sessions in the ESC and STR groups. The other inclusion criterias 11

2 AZHAR MZ et al. include; age between 18 to 50, ability to communicate well, cooperation to carry out sessions in a group for one hour per week. The exclusion criterias include having other psychiatric disorders besides depression, eg. Neuroses or Axis II traits or disorders. All patients gave informed consent to enter the study. They were dropped from the study if they requested to be included in either group or if the medication needed to be changed or if they missed therapy sessions more than once. The duration of inclusion into the study was from January 2004 until June All together 33 patients were recruited for the STR group, 32 for the ESC group and 31 for the FXT group. Procedure Those in the ESC group received a starting dose of ESC 10 mg. per day. They were seen weekly and the doses were increased as necessary to a maximum of 20 mg./day if no side effects occured. Only two patients needed an increased dose to 20 mg/day. Those in the STR group were treated in a similar manner. They received a starting dose of STR 50 mg. per day. They were seen weekly and the doses were increased as necessary to a maximum of 100 mg/day if no side effects occured. Only three patients needed an increased dose to 100 mg/day. Those in the FXT group received a starting dose of ESC 20 mg. per day. They were seen weekly and the doses were increased as necessary to a maximum of 40 mg/day if no side effects occured. Only two patients needed an increased dose to 40 mg/ day. As mentioned earlier all patients were seen for weekly sessions of CBT but were never given any NFD or any other drugs. All patients were seen weekly for 12 weeks and those in the last first two groups received weekly sessions of CBT for 12 weeks with addition of 3 booster sessions monthly. At weekly meetings and at baseline, a research assistant who was blind to the patients group measured the following tests. The tests were a) the Hamilton Depression Scale (HDS) (4), b) the Beck Depression Inventory (BDI) (5), c) the World Health Organization Quality of Life Scale-Brief Version (WHOQOL-BREF) (6). (This was measured only at baseline and at 12 weeks) Analysis The results of all the tests from the three groups of patients were analyzed statistically using chi square, t test, and Anova.. Results The study was conducted over a period of three and a half years. Altogether each patient could be analyzed after receiving treatment for 12 weeks initially and 6 months after start of treatment for some patients. There were all together 96 patients with 32 patients in the ESC group, 33 in the STR group and 31 in the FXT group. The results are shown in the tables below. Table 1 shows that there was no difference in age between the three groups. There was also no significant difference in baseline measurements of BDI, BAI and QOL between the three groups. However after 12 weeks there was a significant difference in all measurements. All patients improved significantly but patients in the ESC group improved better than those in the other two groups. The QOL score also improved in all groups but there was more marked improvement in the ESC group compared with the other two groups. Table 2 shows the results of the analysis done for the first two groups after 6 months of treatment. There was a significant change in both groups at the end of two months however at the end of 6 months there was no significant difference between the two groups. It was obvious that both groups responded well to treatment but the ESC group showed better improvement at two months while both showed similar improvement at 6 months. The results seemed to indicate that those in the ESC group responded faster than in the STR group. Discussion There are specific measuring tools to measure depression. The BDI and HDS were chosen because they are self-administered, not too time consuming, easy to use by patients and the patients were given CBT, which uses these measurements as part of the therapy recording. Patients with this disorder also tend to have a low level of quality of life. We thought this measure would be useful to assess overall improvements in patients. It is very difficult to measure quality of life because there are numerous scales available but no one scale is comprehensive enough to measure all the aspects we would like to look at. The most easy to use in our patients seem to be the WHOQOL-BREF as it has only 30 questions and takes a short time to administer and is not difficult for the patients to understand. It also covers rather comprehensively most of the domains we would like to measure. 12

3 COMPARISON OF DIFFERENT ANTIDEPRESSANTS AND PSYCHOTHERAPY IN THE SHORT-TERM TREATMENT OF DEPRESSION The findings of significant reduction in practically all measures in all groups were expected as they were all being given standard treatment. Using Anova it was clear that the patients in the ESC group did best while the STR group was second and FXT group third, but all three methods were beneficial for all patients. This could be explained by the anxiety and cognitive symptoms present in these patients. If we assume that depression has a lot of psychological component although it is a biological disorder. The psychological symptoms could be maintained by biological factors and as such the results fit the model. So if psychological treatment is used to treat the core issue of the disorder then the other symptoms which are secondary will improve along of course with the help of drugs. Based on Beck s model of depression (7) the negative thoughts and thinking errors were corrected in all patients. It seems that patients in ESC group responded faster perhaps due to their ability to concentrate better or faster than the other two groups. This could be the result of inherent factors within the drug or reduced side effect profile which we are not able to establish because these issues were not measured. However it would be a good project to look at in the future. The measure of QOL was probably the best measure to look at comparing between the groups as it is the end result that would like to establish at the end of treatment i.e. not just reduction in scores of depression but also increase in QOL scores to indicate actual return to normal life. The ESC group again had the highest score and the highest incremental change in QOL compared to the other two groups. As such again the reason for this could be the faster response of patients to the medication or lowered side effects or other reasons to be discovered. We can only postulate but the obvious message from this study is that patients will respond well and quickly to a combination of psychotherapy and an effective antidepressant and will maintain the response for at least 6 months if booster therapy sessions are conducted together with continued usage of medication. All results seem to favour a combination use of drugs together with psychological treatment. But not all doctors would like to do psychological treatment or is comfortable with its techniques. It can be time consuming and patients may not stay in treatment. So how can we make use of the results of this study? At the present time based on referrals, our experience tells us that in Malaysia the majority of family physicians and general practitioners use a SSRI to treat depressive disorders. These are very good drugs which help to calm the patient and has a reasonably fast onset of action however no CBT is given to these patients. It might be useful to refer the cases for CBT in those that do not respond after a few weeks. Otherwise they could use the result of this study to select the best SSRI for their patients. It is important for clinicians to understand that depressive disorder can severely affect the daily life of sufferers. It is well known that suicide rates in depression can reach a rate of 20% or higher (8). As such this condition must be aggressively treated. As most patients see their family physicians or general practitioners initially it is highly important that the family doctor makes the right diagnosis and institutes the right treatment. As can be seen from the results, the SSRIs have significant positive results on the patients. However the improvement were shown after 12 weeks of treatment. It is therefore very important for family physicians (FP) to be patient when using this drug. Several studies have indicated that CBT + SSRIs are useful or better than CBT alone in treating anxiety (9, 10). As such the FP should attempt to use antidepressants especially SSRI in the treatment of major depression. Its efficacy has been proven by many studies over time. The only drawback is that it takes time to work. Patients with depression have been shown to be particularly sensitive to physical symptoms and medication effects (11). The serotonin reuptake inhibitors (SSRIs) have an improved tolerability over the traditional tricyclics and most side effects resolve over time and safety in the medically ill and with overdoses have been established (12). Depression is also not an acute condition but is really a chronic and recurring condition requiring long-term management. As such an SSRI is more acceptable. Treatment should ideally combine psychological treatment with SSRI. Concomitant use of a benzodiazepine if no psychological treatment is used may be helpful but the duration of use should not exceed 2 to 3 weeks. The dose that makes the patient recover should be continued for at least one to two years although studies are still being conducted to ascertain this. If symptoms persist then the obvious thing is to continue treatment or to add psychological treatment. It is not uncommon for FP to conduct psychological treatment. Studies in United Kingdom and Germany (13, 14) have shown that FP can be trained and have shown remarkable results using CBT in depressive patients. In Malaysia most patients also have somatic complaints and these are the initial complaints that take 13

4 AZHAR MZ et al. them to see FPs or GPs There have been several models described but the one the author is most used to is the one by Paul Salkovskis (15). Central in the CBT conceptualization of somatic symptoms is the way patients think about bodily sensations. Beliefs that patient have about the nature of their symptoms can result in a confirmatory bias with respect to illnessrelated information. As a result, such patients selectively notice and remember information that is consistent with their beliefs about their problems. If benign bodily sensations are regarded as being symptomatic of disease, several consequences ensue. First, patients will experience emotional distress, which may cause further bodily sensations. Second, increased attention will be paid to these sensations. Third, the type of behaviours adopted to cope with the symptoms may be dysfunctional in that they act to exacerbate the problem rather than relieve it. Fourth, other people including doctors may respond to patients in a way that intensifies, rather than reduces their concern with disease, attention to bodily sensations and dysfunctional coping. All these processes may become linked in selfperpetuating vicious circles. Patients with somatic symptoms commonly believe that their symptoms have a physical cause. Functional somatic symptoms have been found to be associated with both anxiety and depression which are consequences of the dread or false beliefs of having a disease. Thus with an understanding of this hypothesis, the doctor can modify his/her therapy technique to treat these patients. Using actual CBT techniques will obviously be difficult but counseling using CBT hypothesis might suffice in most patients while the more resistant ones can be sent for further management to a psychiatrist or psychotherapist. Besides the CBT model for depression is very easy to grasp and can be used to treat all patients since depression is the Table 1 : Treatment types received by patients and the results of BDI, BAI, and QOL at baseline and at end of 12 weeks. Treatment Age BDI BDI BAI BAI QOL QOL types Mean pre 12 Pre 12 Pre 12 (sd) Rx sess Rx sess Rx sess CBT + ESC (6.25) (2.15) (2.89) (2.7) (3.97) (3.78) (2.91) CBT + STR (6.17) (3.26) (3.86) (2.36) (4.22) (4.11) (4.32) CBT + FXT (6.76) (1.89) (2.54) (2.3) (1.95) (4.16) (3.63) BDI ; Beck Depression Inventory BAI ; Beck Anxiety Inventory QOL; WHO Quality of life Brief Version Scale Table 2 : Treatment types received by patients and the results of HDS at baseline, at end of 12 weeks and at the end of 6 months. Treatment type Total patients HDS mean HDS mean HDS mean 2 weeks 12 weeks 6 months CBT + ESC CBT + STR NS P<0.001 NS HDS ; Hamilton Depression Scale NS ; Not significant 14

5 COMPARISON OF DIFFERENT ANTIDEPRESSANTS AND PSYCHOTHERAPY IN THE SHORT-TERM TREATMENT OF DEPRESSION main symptom present in the patients. Also when used in combination, the dose of the drug can be reduced and thereby reduce the possibility of side effects which could further aggravate the misinterpretation beliefs patients hold regarding their health. References 1. Beck AT, Rush AJ, Shaw BF, Emery G. Cognitive Therapy of Depression, Guilford Press, New York Azhar MZ. Cognitive Psychotherapy Experience with Kelantan Clients. Medical J. of Malaysia 1998; 53(2): APA. American Psychiatric Association, Diagnostic and Statistical Manual of Mental Disorders- Revised (4th. Edition), Washington D.C., APA, Hamilton M. A Rating Scale for Depression. Journal of Neurology, Neurosurgery and Psychiatry 1960; 23: Beck AT, Ward CH, Mendelson M et al. An Inventory for Measuring Depression. Archives of General Psychiatry 1961;4: The WHOQOL Group. Development of the World Health Organization WHOQOL-BREF Quality of Life Assessment. Psychological Medicine 1988; 28: Beck AT, Rush AJ, Shaw BF, Emery G. Cognitive Therapy of Depression, Guilford Press, New York Rihmer Z. Suicide Risks in Mood Disorders. Curr Opin Psychiatry 2007; 20(1): Sharp EA. Comparison of Fluvoxamine and CBT and Placebo in Panic Disorder, Psychological Medicine 1996; 53: Azhar MZ. Comparison of Fluvoxamine Alone, Fluvoxamine and Cognitive Psychotherapy and Psychotherapy Alone in the Treatment of Panic Disorderin Kelantan Implications for Management by Family Doctors. Med. J. Malaysia 2000; 55(4): Jones LR, Mabe III, Riley WT. Illness Coping Strategies and Hypochondriacal Traits among Medical Inpatients. Int. J. of Psychiat. in Med. 1989; 19: Fontaine R, Ontiveros A, Elie R et al. A Double- Blind Comparison of Nefazodone, Imipramine, and Placebo in Major Depression. J. Clin. Psychiatry 1994; 55(6): Linden M. Cognitive Behaviour Therapy under Conditions of Routine Treatment in the General Health Care System. Behav. & Cog. Psychotherapy 1996; 24: Scott CS, Scott JL, Tacchi MJ, et al. Abbreviated Cognitive Therapy for Depression: A Pilot Study in Primary Care. Behav. & Cog. Psychotherapy 1994; 22: Salkovskis PM. Somatic Problems. In KE Hawton, PM Salkovskis, J Kirk and DM Clark (Eds.) Cognitive Behaviour Therapy for Psychiatric Problems: A Practical Guide, Oxford: Oxford University Press,