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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 7 of 7. This is the beginning of the thread.
Posted by Mishal on June 17, 2007, at 3:20:01
Well, my pdoc gave me Buspar 5mg twice daily. This is my seventh day on it. I already feel emotive and irritable. Buspar is the worst medicine of all I have taken. The worst in giving me the most black mood I have ever experienced.My next appointment is a week apart. What should I ask my doc to augment my prozac? Please help..
Posted by Nathan_Arizona on June 17, 2007, at 10:08:41
In reply to To Augment Prozac: What is best?, posted by Mishal on June 17, 2007, at 3:20:01
Provigil has been used with SSRI's to boost their effect - although this is still considered (I think) an off label use of provigil.
What are your symptoms?
Posted by Phillipa on June 17, 2007, at 11:26:50
In reply to Re: To Augment Prozac: What is best?, posted by Nathan_Arizona on June 17, 2007, at 10:08:41
Providgil boosts their effects? Love Phillipa
Posted by Jesus is Savior on June 17, 2007, at 12:39:25
In reply to To Augment Prozac: What is best?, posted by Mishal on June 17, 2007, at 3:20:01
>
> Well, my pdoc gave me Buspar 5mg twice daily. This is my seventh day on it. I already feel emotive and irritable. Buspar is the worst medicine of all I have taken. The worst in giving me the most black mood I have ever experienced.
>
> My next appointment is a week apart. What should I ask my doc to augment my prozac? Please help..
>How high of a dose are you on right now (Prozac)?
-MJ
Posted by temoigneur on June 17, 2007, at 15:40:02
In reply to To Augment Prozac: What is best?, posted by Mishal on June 17, 2007, at 3:20:01
Hi Mishal... there's a number of common augmentation meds I'm aware of... the two that are the best studied, but less commonly used are lithium and T3 (triiodothyroxine). For me, lithium just made me tired... and it can actually cause among other things, thyroid dysfunction. If your in a pinch to get the prozac working quickly, i would be tempted to try T3... it's not done as commonly anymore, as there's an issue with bone density loss, which you may be able to take supplements for, but is reported to be effective and quick. If you want I've posted an article on T3 augmentation from a sound medical journal. I have an article at home detailing other augmentation options... that I'll try and remember to post. All the best,
Ben
Other meds used to augment antidepressants are Wellbutrin, pindolol, atypical antipsychotics, benzodiazepines, - all with very different and sometimes crude ways of influencing neurochemistry.
T3 augmentation of SSRI resistant depression
Gebrehiwot Abrahama, b, , , Roumen Milevc, d and J. Stuart Lawsond
aDepartment of Psychiatry, University of Toronto, ON, Canada
bMood and Anxiety Unit-Inpatient, Centre for Addiction and Mental Health, Toronto, ON, Canada
cDivision of Adult Treatment and Rehabilitation Psychiatry, Department of Psychiatry, Queen's University, Providence Continuing Care Centre, Mental Health Services, Kingston, ON, Canada
dAdult Treatment and Rehabilitation Services, Providence Continuing Care Centre, Mental Health Services, Kingston, ON, Canada
Received 8 September 2005; revised 23 December 2005; accepted 6 January 2006. Available online 17 February 2006.Abstract
Purpose of study
To investigate whether the addition of triiodothyronine (T3) helps relieve depressive symptoms in non-hypothyroid major depressive disorder patients who failed to respond to an adequate course of standard SSRI antidepressant treatments.
Methods
Patients who fulfilled the DSM-IV criteria for non-psychotic major depression, able to give informed consent, and failed to show satisfactory antidepressant response after a minimum of six weeks adequate treatment were recruited. To enter the study their Hamilton Depression (17-item HAMD) score had to be 18 or more, thyroid-stimulating hormone (TSH) value within the normal range, and a normal thyrotropin releasing hormone-stimulation test (TRH-ST). All patients continued taking the same SSRI which they had been taking before they entered the study. At the completion of TRH-SH they were all started on 25 μg of T3 and the dose was increased to 50 μg within a week when tolerated; they continued the combination of T3 and the SSRI for a minimum of three weeks.
Results
Twelve patients, comprising eight females and four males, entered the study. One female patient withdrew during the first week of side effects, eleven patients completed the trial. The patients ranged from 26 to 77 years of age, with the mean age for males and females being 52.3 and 45.1 years, respectively. Five patients were taking sertraline (mean dose = 130 mg/day) and 4 were taking citalopram (mean dose = 50 mg/day), two were on fluvoxamine (150 mg/day) and one patient was on 40 mg of paroxetine. The women took a mean daily dose of 40.6 μg of T3 for a mean duration of 3.75 weeks, while the men were on a mean daily dose of 43.8 μg of T3 for 3.5 weeks. T3 augmentation was associated with a statistically significant drop (p < .003) in the mean HAMD at end of the three weeks compared to baseline scores. Five patients (42%) showed ≥ 50% improvement on HAMD scores, with three achieving full remission (HAMD scores ≤ 7) at the end of the study. There were no reliable differences between responders and non-responders in baseline HAMD scores, number of previous antidepressant trials, gender or Δmax TSH.
Conclusion
T3 augmentation resulted in improvement of mood scores. The responders' rate of 42% in our study is comparable to the response rates reported using T3 or lithium to augment tricyclic antidepressants or other combination strategies used to treat resistant depression. Even though one patient withdrew prematurely due to side effects, the remaining 11 patients tolerated the addition of T3 very well. With the availability of T3, a viable, safe, inexpensive and effective augmentation treatment, the recent trend of replacing T3 with other novel strategies appears unwarranted.
Keywords: T3; Augmentation; SSRI; Resistant depression
Article Outline1. Introduction
2. Subjects and methods
2.1. Patients
2.2. Laboratory tests
2.3. Outcome measures
2.4. Treatment regimen
2.5. Statistical analysis
3. Results
4. Discussion
References1. Introduction
Despite significant advances in the treatment of depression, many patients fail to respond to treatment with the recommended regimens of standard antidepressants. Selective serotonin reuptake inhibitors (SSRIs) are now commonly used in the treatment of major depression. In all patients starting treatment, the intent-to-treat response rate is about 50% (Nelson, 1998). The other 50% will need some changes in the treatment, to obtain resolution of the depressive illness.
Triiodothyronine (T3) has been shown to accelerate and potentiate the clinical response to tricyclic antidepressant (TCA) treatment in depressive disorders (Moreau et al., 2001), even though the exact mechanisms underlying therapeutic effects of T3 are still unknown. Aronson et al. (1996), in a meta-analysis, reported that depressed patients treated with T3 augmentation of TCAs were twice as likely to respond, as were controls. Gitlin and associates (1987) found no difference in response when T3 or placebo was added to a TCA, while Joffe et al. (1993) reported that both lithium and T3 augmentation were superior to placebo with more than 50% of patients responding to active treatment. Although T3 augmentation may be an effective and inexpensive method of increasing response rates and decreasing the severity of depression in patients refractory to TCA therapy (Goodwin et al., 1982 and Souche et al., 1991), its usefulness in augmenting SSRIs has not been well documented. Two studies (Agid and Lere, 2003 and Iosifescu et al., 2005) and a few case reports of patients who responded to T3 augmentation after failing to show any response to an SSRI have been reported in the literature (Crow et al., 1990, Gupta et al., 1991 and Joffe, 1992).
The purpose of the present study was to determine if statistically reliable improvement in the form of lower HAMD scores could be shown to follow the use of adjunctive T3 in SSRI resistant patients.
2. Subjects and methods
2.1. Patients
The sample consisted of 12 consecutive patients fulfilling clinical DSM-IV criteria for non-psychotic non-bipolar major depressive episode who gave written informed consent to the study. The subjects were non-responders after receiving adequate treatment for more than six weeks (range 6–14 weeks) with an SSRI. To enter the study their Hamilton Depression Rating Scale (HAMD) (Hamilton, 1960) score had to be at least 18, and have a normal TRH stimulation test and thyroid stimulating hormone (TSH) value.
2.2. Laboratory tests
After an overnight fast, a thyrotropin releasing hormone-stimulation test (TRH-ST) was conducted in the morning with the placement of an 18 gauge intravenous catheter in the antecubital fossa. Blood sample was taken for baseline TSH, and antimicrosomal and antithyroglobulin antibodies. Protirelin TRH (Relefact, Hoechest-Roussel Canada, Inc., Laval, Quebec) 500 μg was then injected slowly over 30 s. Post-TRH blood samples were drawn for TSH at + 15, + 30, + 45 min. Vital signs were monitored during the study. TSH was measured by a two-site cheminoluminescent immunoassay on the ACS-180 analyzer (Ciba Corning, Medfield, Mass.) (Klee and Hay, 1987).
Antimicrosomal and antithyroglobulin antibodies were measured by Commercialized Kits (Murex Biotech Ltd., Dartford, England) to further ensure the exclusion of patients with thyroid disorder.
2.3. Outcome measures
Each patient underwent a complete medical and psychiatric evaluation at baseline. Patients were administered the 17-item HAMD at baseline before the addition of T3 and at the end of at least 3 weeks of T3 augmentation. Improvement was defined as a drop in HAMD of 25–49%, response ≥ 50% from baseline scores, and remission HAMD ≤ 7.
2.4. Treatment regimen
All patients continued taking the same SSRI at the same dosage as before they entered. After the completion of the TRH-ST all patients were started on 25 μg of T3 and the dose was increased to 50 μg within a week when tolerated. They continued to take the SSRI and T3 for a minimum of a 3-week period.
2.5. Statistical analysis
Paired sample t tests were conducted to test for improvement in mood as assessed by HAMD score from baseline to end of the study. Additional contrasts were done to compare mean scores between baseline TSH and TSH at T15, T30, and T45.
3. Results
Twelve Caucasian patients (8 females and 4 males) were enrolled, but only 11 completed the study as one female patient withdrew during the first week complaining of increased anxiety and agitation. The patients ranged from 26 to 77 years of age. The mean age for males was 52 ± 16 years and for females 45 ± 18 years. Among the 12 patients 5 were taking sertraline (mean dose = 130 (range 100–200) mg/day), 4 were taking citalopram (mean dose = 50 (range 40–60) mg/day), two were on fluvoxamine (mean dose = 150 mg/day), and one patient was on 40 mg/day of paroxetine. The women took a mean dose of 40.6 μg of T3 for a mean duration of 3.75 weeks while the men were on a mean dose of 43.8 μg/day of T3 for 3.5 weeks; range for both sexes was 25–50 μg given for 3–4 weeks.
The patients were all treatment resistant, 4 in stage 2, 7 in stage 3 and 1 in stage 4 (Thase and Rush, 1997) before the current trial for same episode. Two patients who had been taking olanzepine for several months continued at the same dose. Lab results indicated that none of our patients had abnormal TSH values at baseline, or elevated titers of the thyroid antibodies. Using the criteria of Δmax TSH > 25 MIU/L (Degroot, 1989) (delta max TSH defined as the peak TSH value after TRH stimulation minus the baseline TSH value pre-TRH-ST), none of our patients met the criteria for subclinical hypothyroidism.
T3 augmentation was associated with partial improvement (Hirschfeld et al., 2002) in 2 patients (HAMD scores dropping by 27% and 38.5%), response in 5 (> 50% drop in HAMD) and remission in three of the 5 (HAMD ≤ 7) (Prien and Levine, 1984) during the three weeks of T3 augmentation. Overall HAMD dropped from a mean of 27 ± 4 at baseline to a mean of 17 ± 8 at end of study (p < 0.003) (Fig. 1). There was no correlation between responders and non-responders in baseline HAMD scores, number of previous antidepressant trials, or delta max TSH.
Display Full Size version of this image (31K)
Fig. 1. HAMD scores before ▪ and after treatment with T3.
Analysis of changes in HAMD using two-tailed paired t-tests were conducted on both the arithmetical differences between pre- and post-treatment scores (HAMDpre–HAMDpost) and percent change (100 [1 − Post / Pre]). The results showed reliable decline in HAMD scores for both algorithms (p = .003 and .004, respectively).We modeled the TSH response to TRH challenge in each patient using a three-parameter exponential model. The three parameters corresponded roughly to baseline, maximum response and rate of response, respectively. None of the parameters was predictive of baseline HAMD, final HAMD or HAMD increment.
4. Discussion
T3 augmentation resulted in improvement of mood scores in 58% of the patients who participated in this open-label study. Although there is an overwhelming amount of evidence indicating the effectiveness of lithium augmentation of antidepressants for treating resistant depression and promising research of thyroid hormone augmentation of TCAs, these strategies are underutilized (Shelton, 2003).
There are few case reports on T3 augmentation of SSRIs in resistant depression. Agid and Lere (2003) found 40% of SSRI resistant depressed patients responded to a two-week treatment with T3 and in this group gender was a significant predictor in that none of the male patients responded while 10 of the 16 females responded. They also found that responders had higher levels of TSH compared to non-responders, even though the TSH levels were within the normal range. Our response rate of 42% (2 responders and 3 remitters) is comparable to the response rates reported by Agid et al. as well as with other augmentation or combination strategies used to treat resistant depression, but lower than that of Iosifescu et al. (2005) who reported a response in 35% and remission in 30% of their SSRI resistant patients. The higher rate of response reported by Iosifescu et al. may be a function of using higher dose of T3 for longer duration. On the other hand, Appelhof et al. (2005) reported more adverse reaction occurring with T3 addition to SSRI, but no benefit even when given at similar treatment conditions as Iosifescu et al. In contrast to the Agid study, our study found no relationship between TSH level and response to T3 augmentation nor was there any relation between the gender of our patients, or other clinical variables and their clinical response. One possible explanation for Agid's finding of relationship between higher normal TSH and response to T3 could be that these patients may have been suffering from a subclinical hypothyroid state. This is further supported by their observation that only female patients appeared to benefit from T3 augmentation, the very group that are at increased risk of suffering from hypothyroidism (Redmond, 2004). Joffe et al. (1993), using T3 to augment TCAs, reported a response rate of 59%. In contrast Birkenhager et al. (1997) found no evidence for the efficacy of adjunctive T3 treatment to tricyclic antidepressants in severely depressed inpatients. The lack of response in their sample was believed to be related to the absence of exaggerated TSH response to TRH-ST. Similarly, Targum et al. (1984) also found that response to T3 augmentation was preferentially found in patients with an exaggerated release of TSH after TRH stimulation. The present study found T3 to be efficacious in patients who did not demonstrate subclinical hypothyroidism as evidenced by lack of exaggerated TSH response to TRH-ST. Our finding of absence of a relationship between response and TRH-ST results is in keeping with several other studies (Gitlin et al., 1987 and Thase et al., 1989).
A more novel augmentation strategy utilizing atypical antipsychotics for resistant depression reported 60% of patients responding when olanzepine was added to fluoxetine (Shelton et al., 2001). Use of atypical antipsychotics can, however, be limited by adverse effects such as extrapyramidal symptoms, weight gain, somnolence and metabolic abnormalies (Weizerman and Weizman, 2001).
The mechanism of action of T3 augmentation on antidepressants is not clearly understood. Several explanations have been advanced, including treating possible subclinical hypothyroidism. In this study none of the patients had an exaggerated TSH response to TRH-ST, excluding the possibility that we were treating hypothyroid states. Other mechanisms which have been proposed include actions via nuclear receptors on gene expression, effects on membrane-bound receptors, and actions at the second-messenger level (Newman et al., 2003).
This prospective, open-label trial has significant limitations. In addition to a small sample size, there is no control group against which to compare the results; thus alternative explanations for the positive results are plausible. For example, it is possible that the improvement can be related to delayed response to continued treatment with the SSRIs, and not related to the addition of T3. Most of these treatment refractory patients had, however, been on several different antidepressants and at least six weeks on a therapeutic dose of the current SSRI without improvement in their mood. Patients who do not show response within the first few weeks are unlikely to show robust response by simply prolonging the duration of treatment with the same agent (Nierenberg et al., 2000 and Stassen et al., 1993). Quitkin et al. (1996) recommended treatment be changed after 4 weeks if there was no apparent improvement. The American Psychiatric association's practice guideline(2000) also indicates 4–6 weeks of treatment with an adequate dose to be sufficient, after which the trial can be declared to have failed. Thus, our patients’ response is most likely related to the addition of T3.
In conclusion, T3 augmentation of SSRI resistant depression should be considered as one of the viable, safe and inexpensive tools in our armamentarium for treating these very ill patients, notwithstanding current trends to use other novel strategies (Mischoulon et al., 2000). Both a larger sample and controlled studies are needed to determine whether our observations prove reliable.
Posted by med_empowered on June 17, 2007, at 21:21:51
In reply to T3 augmentation of SSRI resistant depression » Mishal, posted by temoigneur on June 17, 2007, at 15:40:02
and what's chosen will depend on your symptoms and your doc's preferences. If you're agitated, there's benzos and low-dose neuroleptics, maybe the anticonvulsants (tegretol, depakote, etc.). Anxiety can be treated with benzos or neuroleptics or possibly hydroxyzine (vistaril).
If you're apathetic and lethargic, you might want to try wellbutrin, provigil, or a more traditional stimulant, like ritalin or dexedrine or adderall.
Sometimes adding a tricyclic drug helps.
Lithium and T3 are both options. Making sure your nutrient levels (folic acid, for instance) are up to snuff is important; you may want to supplement.
If you have a history of drug/alcohol abuse, some of these options might not be made available to you. Then again...some docs will still use controlled substances with former drug users with monitoring. So it really depends.
BuSpar pretty much sucks. I'm not entirely sure why its still around: you'd think p-docs would've caught on by now. Anyway, better luck in the next round.
Posted by Nathan_Arizona on June 18, 2007, at 17:31:02
In reply to Re: To Augment Prozac: What is best? » Nathan_Arizona, posted by Phillipa on June 17, 2007, at 11:26:50
some studies say yes, other studies say marginal improvement.
personally, I went on provigil once when I was at 40 mgs prozac and sleepiness was ruling the day.
It just made me agitated and mad - not sleepy though - certainly not sleepy.
This is the end of the thread.
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