تاثیر دارو درمانی طبیعی همزمان بر روان درمانی از غم و اندوه پیچیده

Abstract Complicated grief (CG) is a debilitating syndrome that can be reliably identified, but there is a paucity of research examining treatment of CG. A targeted psychotherapy for complicated grief (CGT) was recently shown to be efficacious [Shear, K., Frank, E., Houck, P.R., Reynolds, C.F., 3rd, 2005. Treatment of complicated grief: a randomized controlled trial. Journal of the American Medical Association 293, 2601–2608]. We provide a detailed examination of the association of naturalistic pharmacotherapy use with treatment response and study completion in the psychotherapy study. Patients on an antidepressant medication were more likely to complete a full course of CGT (91% vs. 58% completed), while antidepressant use had no effect on completion rates for the comparator, interpersonal psychotherapy (70% vs. 77%). Our naturalistic data underscore the need for prospective, randomized controlled studies of CG pharmacotherapy and psychotherapy alone and in combination.

. Introduction Complicated grief (CG) is a debilitating syndrome that can be reliably identified. CG is diagnosed when intense grief persists more than 6 months after the loss of a loved one. Symptoms include separation distress (recurrent pangs of painful emotions, with intense yearning and longing for the deceased, and preoccupation with thoughts of the loved one) and traumatic distress (sense of disbelief regarding the death, anger and bitterness, distressing, intrusive thoughts related to the death, and pronounced avoidance of reminders of the painful loss) (Shear et al., 2005). While CG causes significant distress and impairment (Silverman et al., 2000 and Shear et al., 2005), and is associated with excess medical morbidity and suicidality (Prigerson et al., 1997, Prigerson et al., 1999 and Szanto et al., 2006), little is known about its treatment. Pharmacotherapy studies primarily targeting bereavement-related depression found minimal to modest effects of medication on grief (Zygmont et al., 1998, Reynolds et al., 1999 and Zisook et al., 2001). Zisook and colleagues treated 22 individuals who met criteria for a major depressive episode (allowing bereavement) 6–8 weeks after a loss with open-label bupropion, and found significant reduction in depression, with modest though statistically significant concurrent decreases in grief symptoms in this acute period (Zisook et al., 2001). Zygmont and colleagues openly treated 15 individuals with complicated grief 6 to 17 months after a loss with paroxetine (median dose 30 mg/day) for 4 months concurrent with a grief-focused course of psychotherapy and found a similar reduction in grief symptoms as in a historically treated group of 22 individuals who received nortriptyline for bereavement-related depression; however, the study design did not allow separation of paroxetine effects from psychotherapy effects (Zygmont et al., 1998). In the only relevant randomized clinical trial to date, Reynolds and colleagues examined the impact of nortriptyline, interpersonal psychotherapy or the combination on bereavement-related major depressive episodes in 80 patients aged 50 and older, and found that while there were antidepressant effects in this population treated with nortriptyline, neither interpersonal psychotherapy nor nortriptyline led to a significant reduction in grief symptoms (Reynolds et al., 1999), consistent with an earlier open pilot study of nortriptyline in bereavement-related depression that failed to reduce grief intensity (Pasternak et al., 1991). We therefore developed complicated grief therapy (CGT), which was demonstrated efficacious compared with interpersonal psychotherapy (IPT) in the first randomized controlled trial (RCT) of a treatment for CG (Shear et al., 2005). The active control condition, IPT with a grief focus, followed a standard published manual (Weissman et al., 2000). Briefly, IPT has an introductory phase when symptoms and an interpersonal inventory are reviewed; a middle phase addressing grief symptoms and interpersonal problems (as well as specifically addressing the positive and negative aspects of the patient's relationship with the deceased person), and encouraging participation in satisfying activities and relationships; and a termination phase. CGT similarly followed a manual and consists of an introductory, middle and termination phase. The introductory phase has a greater focuses on psychoeducation about the difference between normal and complicated grief, information about the “dual process” model of adapting to loss including adjustment to loss of the loved one, and an emphasis on personal goals and restoration of life satisfaction. In addition to working directly with personal goals throughout the treatment, the middle phase of CGT included loss-focused elements adapted from exposure therapy techniques, including telling and listening to tapes of the story of the death (“revisiting”), hierarchical exposure to avoided reminders of the loss, direct work with positive and negative memories of the deceased, and an imaginal conversation with the deceased person. CGT and IPT were each 16 sessions in length. In the overall RCT, CGT resulted in a significantly greater proportion of treatment responders than IPT in both the intent to treat (51% CGT vs. 28 IPT, P = 0.02) and the completers only analyses (66% CGT vs. 32% IPT, P = 0.006). Stable medication use was permitted during the psychotherapy study; we previously reported that 45% (43/95) of RCT participants were taking an antidepressant, and initial analyses found non-significant differences in outcome for those on an antidepressant medication (Shear et al., 2005). Given the dearth of information about treatment of CG, we now present detailed secondary analyses of naturalistic pharmacotherapy use and its association with response and completion of CGT and IPT in the trial. To our knowledge, this is the first study to examine the impact of concurrent medication use on two different types of psychotherapy.

3. Result 3.1. Pharmacotherapy use and baseline characteristics in the randomized trial (n = 95) Demographic data have been previously published (Shear et al., 2005). Briefly, the sample was 87% female and 76% Caucasian, with a mean (SD) age of 48.4 ± 12.7 years, and a mean baseline ICG score of 45.4 ± 8.6. With regards to comorbidity, 70.5% of the sample had a current comorbid mood or anxiety disorder. Current major depressive disorder (MDD) was diagnosed in 46.3% of the sample, while 59.0% had at least one current anxiety disorder (48.4% current posttraumatic stress disorder, 10.5% current panic disorder, 6.3% current obsessive-compulsive disorder, 3.2% current social anxiety disorder). Psychiatric medication use was common, with 52.6% (n = 50) on at least one psychiatric medication, 20% (n = 19) on a benzodiazepine, 6.3% (n = 6) on an anticonvulsant, 4.2% (n = 4) on an antipsychotic, and 45.3% (n = 43) on an antidepressant. Of note, of those on an antidepressant, 32% were on more than one antidepressant, 51% were on at least one other agent, and 35% were taking a concurrent benzodiazepine. There was no significant difference in baseline CG severity for those on an antidepressant (mean ICG = 45.9 ± 9.5) vs. not (ICG = 44.3 ± 8.6). There was, however, significantly greater antidepressant use in those with at least one comorbid mood or anxiety disorder (53.7% (36/67)) compared with those without (25% (7/28): Fisher's Exact Test, P = 0.013). More specifically, 61.4% (27/44) of those with comorbid current MDD were on an antidepressant, compared with only 31.4% (16/51) without (Fisher's Exact Test, P = 0.004), while 57.6% (38/66) with lifetime MDD were on an antidepressant currently compared with 17.2% (5/29) of those without. 3.2. Pharmacotherapy and treatment outcomes in the psychotherapy trial Table 1 presents psychotherapy response rates among those with and without concurrent pharmacotherapy. For the full study sample (n = 95), current antidepressant use was significantly associated with a more than doubling of the odds of treatment response in both univariate (OR = 2.4) and adjusted (OR = 2.7) analyses (see Table 1). For the CGT group alone, those on an antidepressant had a 61% response rate compared with 42% of those not; however, no psychiatric medication was associated with a statistically significant difference in response rate to CGT in either univariate or demographic and comorbidity adjusted analyses (see Table 1). By contrast, our data suggest current concomitant medication use (notably benzodiazepines) was of significant benefit for the individuals with CG receiving IPT (see Table 1). Table 1. Association of current naturalistic pharmacotherapy with treatment response to complicated grief therapy (CGT) and to interpersonal therapy (IPT) in a psychotherapy trial of complicated grief CGI-I response rate Overall (n = 95) CGT (n = 49) IPT (n = 46) Meds present Meds absent Univariate OR 95% CI Adjusted OR 95% CI Meds present Meds absent Univariate OR 95% CI Adjusted OR 95% CI Meds present Meds absent Univariate OR 95% CI Adjusted OR 95% CI At least one medication 46.8% 22/47 33.3% 16/48 1.8 0.77–4.0 2.0 0.82–4.8 53.6% 15/28 47% 10/21 1.1 0.35–3.3 1.0 0.31–3.4 38.1% 8/21 20.0% 5/25 2.8 0.75–10.5 3.9 t 0.82–18.7 At least one benzodiazepine 50.0% 10/20 37.3% 28/75 1.7 0.62–4.5 1.7 0.59–4.8 44.4% 4/9 52.5% 21/40 0.7 0.17–3.1 0.6 0.14–3.0 50.0% 5/10 22.2% 8/36 4.8⁎ 1.13–20.4 5.3⁎ 1.03–27.4 At least one antidepressant 51.2% 22/43 30.8% 16/52 2.4a 1.02–5.5 2.7a 1.1–6.8 60.9% 14.23 42.3% 11/26 2.1 0.68–6.7 2.1 0.59–7.3 40.0% 8/20 19.2% 5/26 2.8 0.75–10.5 4.8t 0.90–25.6 Table Notes: Odds ratio (OR) and 95% confidence interval from logistic regression model of Clinical Global Impression of Improvement (CGI-I) responder status: Univariate OR presented first; adjusted OR includes adjustment for age, gender, race and psychiatric comorbidity. a Denotes P value < 0.05 for OR of medication covariate in regression model. t = statistical trend (P < 0.10). Table options 3.3. Effect of pharmacotherapy on dropout rate in the psychotherapy trial Data regarding the association of pharmacotherapy with study completion are presented both univariately and adjusted for psychiatric comorbidity in Table 2. Overall, there was no difference in study completion rates for CGT (73.5%) compared with IPT (73.9%). However, use of antidepressants was associated with significantly higher odds of CGT completion compared with those not on an antidepressant in both univariate (OR = 7.7) and comorbidity adjusted analyses (OR = 6.3: see Table 2). The presence of antidepressants did not, however, impact IPT completion. Benzodiazepine use was not associated with study completion (see Table 2). Table 2. Association of current naturalistic pharmacotherapy with completion rates for complicated grief therapy (CGT) and interpersonal therapy (IPT) in a psychotherapy trial of complicated grief Overall completion rates (n = 95) CGT completion rates (n = 49) IPT completion rates (n = 46) Meds present Meds absent Univariate OR 95% CI Adjusted OR 95% CI Meds present Meds absent Univariate OR 95% CI Adjusted OR 95% CI Meds present Meds absent Univariate OR 95% CI Adjusted OR 95% CI At least one medication 75.5% 37/49 71.7 33/46 1.2.49–3.02 1.2 0.46–3.0 78.6% 22/28 66.7% 14/21 1.8 0.51–6.6 1.5 0.38–5.6 71.4% 15/21 76.0% 19/25 0.8 0.21–3.0 1.0 0.25–4.0 At least one benzodiazepine 73.7% 14/19 73.7% 56/76 1.0 0.32–3.1 1.0 0.32–3.1 66.7% 6/9 75.0% 30/40 0.7 0.14–3.2 0.7 0.14–3.7 80.0% 8/10 72.2% 26/36 1.8 0.33–9.8 1.6 0.28–9.25 At least one antidepressant 81.4% 35/43 67.3% 35/52 2.1 0.81–5.6 2.1 0.80–5.8 91.3% 21/23 57.7% 15/26 7.7a 1.48–39.9 6.3a 1.18–34.2 70.0% 14/20 76.9% 20/26 0.7 0.19–2.6 0.9 0.21–3.4 Table Notes: Odds ratio (OR) and 95% confidence interval from logistic regression model of completer status: Univariate OR presented first; adjusted OR includes adjustment for psychiatric comorbidity. a Denotes P value < 0.05 for OR of medication covariate in regression model.