Microsoft word - 05=mokhberi

ـــــــــــــــــــــــــــــــــــــــ Original Article ـــــــــــــ
Comparing the Efficacy of add-on Nortryptiline With Triiodothyronine in the
Management of Citalopram-Resistant Depression
___________________________________________________________________________________________
Objective: To manage a treatment resistant depression, clinicians may add a second medication to the first
antidepressant drug. The aim of the current research was to study the outcome of augmentation of citalopram with nortryptiline or triiodothyronine in a randomized clinical trial. Methods: We selected 48 adult outpatients with a diagnosis of non-psychotic major depressive disorder who
had not responded to 12 weeks citalopram therapy (40 mg per day). They were randomly allocated to two groups. One group received nortryiptiline (at a dose of up to 150 mg per day) and the other triiodothyronine (T3) (at a dose of up to 50 µg per day). The remission of depression was defined as a score of 7 or less on the 17-item Hamilton Rating Scale for Depression (HRSD-17). Results: After 8 weeks, the nortriptyline group had a higher remission rate (33.33 %) than the
triiodothyronine group (17.64%). The nortriptyline group, however, had a higher drop out rate due to experiencing more side effects. Conclusion: Augmentation of citalopram with nortryptiline seems to be effective in the management of
treatment resistant depression. However, one should strike a balance between the efficacy and the tolerability of this approach, as there is a higher chance of experiencing side effects by the patients. Iranian Journal of Psychiatry and Behavioral Sciences (IJPBS) , Volume 1, Number 2, Autumn and Winter 2007 : 23-27 . Keywords: Citalopram • Depression • Nortryptiline • Triiodothyronine
•Introduction
antidepressants (11,12). These strategies can also be potentially useful in treating patient resistant to serotonin selective reuptake the investigators to conduct various research projects to explore other strategies of dealing other. The remission rate to a therapeutic with treatment resistant depression. One of plasma level of nortriptyline appears to be these strategies is adding an adjunctive higher than the remission rate to a standard therapy to pre-existing antidepressant. These dose of citalopram, especially in those with include lithium, sleep deprivation, light endogenous or psychotic features. On the other hand, citalopram appears to be better amisulpride (1,2). Some researchers have to assess the effect of combination of them in disorder, clinician often requires more than patients with treatment-resistant depression. one medication to achieve a remission (3-10). Furthermore, the choice of treatment after Frequently, a second medication is added to failure of SSRIs in the treatment of depression augment the first drug (6-8). There is evidence largely depends on the preferences of the to prove the effectiveness of lithium or physician. The STARD (Sequenced Treatment Alternatives to Relieve Depression) trials set out to rationalize the treatment of depression Authors' affiliation : * Department of Psychiatry, Mashad
after the failure of citalopram. When subjects •Corresponding author : Naghmeh Mokhber MD, Assistant
professor of Psychiatry. Fellowship of neuropsychiatry, Mashad citalopram were switched to sustained-release University of Medical Sciences, Ibn-e-sina Hospital, Mashad, Iran. bupropion, sertaline or extended-release Tel : +98 511 7112701 Fax : +98 511 7112723 venlafaxine, remission rates were similar(14,16). Iranian Journal of Psychiatry and Behavioral Sciences (IJPBS) , Volume 1, Number 2, Autumn and Winter 2007 Comparing the efficacy of add-on nortryptiline with triiodothyronine nortriptyline with triiodothyronine when added from all subjects. The ethics committee of (Mashad, Iran) approved the protocol. The trial was performed in accordance with the Materials and Methods
citalopram) were randomized into two groups. psychiatric outpatient clinics of two teaching One group (N=28) received nortritptyline hospitals (Ibn-e-sina and Ghaem) in Mashhad (150mg/day) and the other triiodothyronine (Iran) took part in the study in 2005. Seven (50µg/day, N=20). The add on medications subjects dropped out of the study due to were initiated at low dose and then titrated up adverse events (table 1). All patients met to the final dose over a period of 4 weeks. The dose then remained the same till the end of depressive disorder. To enter the study, a the study. During the trial, the citalopram patient’s thyroid-stimulating hormone (TSH) value had to be within the normal range. Lorazepam up to 4mg/day was permitted on an as required regime (prn) to tackle extreme improvement in depressive symptoms after 8 agitation or insomnia during the first two weeks of the study. Four patients could not continue the trial because they developed side effects to nortriptyline (sedation, drowsiness and gastrointestinal upset). Three patients Table 1. Demographic characteristics of the participants
withdrew from the triiodothyronine group Characteristics Both
Nortriptyline
Triiodothyronine
because of a worsening in their symptoms. Age (years ± SD)

Education (years ± SD)
examination and a series of laboratory tests
Male/female (n)
(blood count, fasting blood sugar, liver
Employment status (n)
function tests, kidney function tests, thyroid function test and urine analysis) at baseline. Marital status (n)
Vital signs and side effects to medications interval for the first 4 weeks and then at the
Age at first episode
(mean-years) ±SD
A psychiatrist, using structured clinical HRDS-17 Scores
at study entry (±SD)
interview for DSM-IV (SCID), interviewed the patients and their family at baseline and at the final visit. A single psychiatrist performed all ratings to reduce inter-rater error. In Subjects with any other DSM-IV diagnosis addition, patients along with their families requiring psychological or pharmacological information on demographic characteristics prior to start of the study were other exclusion Rating Scale for Depression (HRSD-17) (17). criteria. Women of childbearing potential who A remission was defined as a score of 7 or were without adequate contraception were less on the HRSD-17. The primary outcome measure was baseline versus endpoint change Iranian Journal of Psychiatry and Behavioral Sciences (IJPBS) , Volume 1, Number 2, Autumn and Winter 2007 in the HRDS-17 scores. Both the psychiatrist was greater in nortriptyline group (33.33%) than triiodothyronine group (17.64%). Other treatment groups throughout the study period. triiodothyronine (T3) helps relieve depressive symptoms in non-hypothyroid major depressive We performed the statistical analysis on all disorder patients who failed to respond to patients including those who had dropped out. antidepressant treatments(18). Hypothalamic- depression scores between groups. For all analyses, p<0.05 was defined as statistically significant. All statistical analyses were erythrocytes and membrane lipids have a role performed using statistical package for social in the development and treatment of affective disorders. The change in the function of the alteration of membrane fluidity and/or transporter-lipid interactions Other studies have shown that the addition study. Tolerability and adverse events are of citalopram to nortriptyline led to clinical Table 2 . Tolerability and adverse events
that the antidepressant effects are mediated by both serotonin (5-HT) and norepinephrine Nortriptyline
Triiodothyronine
Worsening of depression
0 3 researchers have tried to augment the efficacy Sedation and drowsiness
3 0 of SSRIs by adding an antipsychotic to the Gastrointestinal distress
norepinephrine reuptake inhibitors (SNRIs) may be used as an alternative treatment for differences between two groups regarding depressed patients who do not tolerate or age, gender or educational level. The mean of baseline depression score was similar in both conventional antidepressant (24). Because the groups (table 1). However, a significant diffusion of NE may be spatially limited by change in total mean scores was observed serotonin transporters, the SSRIs, despite their following treatment in both groups (p<0.05) selectivity, might enhance not only serotonergic (table 3). The mean change of total depression but also noradrenergic neurotransmission, score was greater in nortriptyline group which might contribute to their antidepressant compared to triiodothyronine group (p<0.05). action (25). Furthermore, other studies show that NE plays an important role in mediating acute behavioral and neuro-chemical actions Table 3 . Treatment outcomes
Nortriptyline
Triiodothyronine
SSRIs (26) and use of nortriptyline might HRDS-17 remission rate
Our study has several limitations. Firstly, at the end of study (%) *
HRDS-17 Scores at the
due to the relatively small sample size, the end of study (±SD) *
power of the study is limited. Secondly, there was no placebo control group in the study. In our study seven patients could not complete Discussion
the trial due to the side effects. In addition, subjects were selected from academic psychiatric outpatient clinics and may not be measured by a reduction in HRSD-17 scores representative of community patients. Our Iranian Journal of Psychiatry and Behavioral Sciences (IJPBS) , Volume 1, Number 2, Autumn and Winter 2007 Comparing the efficacy of add-on nortryptiline with triiodothyronine study results cannot be generalized to patients with psychotic symptoms. Finally, we could not monitor the blood levels of the drugs due for major depressive disorder: a literature approach to improve practice. Psychother Acknowledgments
8. Rush AJ, Fava M, Wisniewski SR, Lavori committee of Mashad University of Medical Sciences. The authors would like to thank Dr. Mohamad Taghi Shakeri for their invaluable al. Clinical results for patients with major References
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