Neurostimulation is rapidly emerging as an important treatment modality for psychiatric disorders... more Neurostimulation is rapidly emerging as an important treatment modality for psychiatric disorders. One of the fastest-growing and least-regulated approaches to noninvasive therapeutic stimulation involves the application of weak electrical currents. Widespread enthusiasm for low-intensity transcranial electrical current stimulation (tCS) is reflected by the recent surge in direct-to-consumer device marketing, do-it-yourself enthusiasm, and an escalating number of clinical trials. In the wake of this rapid growth, clinicians may lack sufficient information about tCS to inform their clinical practices. Interpretation of tCS clinical trial data is aided by familiarity with basic neurophysiological principles, potential mechanisms of action of tCS, and the complicated regulatory history governing tCS devices. A growing literature includes randomized controlled trials of tCS for major depression, schizophrenia, cognitive disorders, and substance use disorders. The relative ease of use an...
Major depression is a common and debilitating illness. Over recent years, new pharmacologic treat... more Major depression is a common and debilitating illness. Over recent years, new pharmacologic treatments have been approved for this disorder, including the atypical antipsychotics. One of the benefits of these medications is their significant efficacy as augmenting agents for unipolar, nonpsychotic major depressive disorder (MDD).Aripiprazole (marketed as Abilify, Bristol-Myers Squibb/ Otsuka Pharmaceuticals) was the first medication of this class approved for adjunctive treatment of MDD, and is the 5th most commonly prescribed medication in the United States in 2010. However, despite the frequency of its use, little has been described regarding events surrounding aripiprazole discontinuation. Here I describe what is, to my knowledge, the first reported case of an aripiprazole discontinuation syndrome. While directly relevant to psychiatrists and behavioral specialists, the symptoms described here are pertinent for internists and neurologists who may encounter this medication in thei...
Academic psychiatry : the journal of the American Association of Directors of Psychiatric Residency Training and the Association for Academic Psychiatry, Jan 16, 2016
Early life stress (ELS) is an established risk factor for psychiatric illness and is associated w... more Early life stress (ELS) is an established risk factor for psychiatric illness and is associated with altered functional connectivity within- and between intrinsic neural networks. The widespread nature of these disruptions suggests that broad imaging measures of neural connectivity, such as global based connectivity (GBC), may be particularly appropriate for studies of this population. GBC is designed to identify brain regions having maximal functional connectedness with the rest of the brain, and alterations in GBC may reflect a restriction or broadening of network synchronization. We evaluated whether ELS severity predicted GBC in a sample (N = 46) with a spectrum of ELS exposure. Participants included healthy controls without ELS, those with at least moderate ELS but without psychiatric disorders, and a group of patients with ELS- related psychiatric disorders. The spatial distribution of GBC peaked in regions of the salience and default mode networks, and ELS severity predicted ...
Relative to HIV-negative adults, HIV+ adults report elevated levels of early life stress (ELS). I... more Relative to HIV-negative adults, HIV+ adults report elevated levels of early life stress (ELS). In non-HIV samples, high ELS has been linked to abnormalities in brain structure and function, as well as increased risk of neuropsychiatric symptoms. Yet, little is known about the neural effects of high ELS, and their relation to elevated neuropsychiatric symptoms, in HIV+ adults. Recent studies have revealed combined effects of HIV and high ELS on amygdala morphometry. Aberrant amygdala activity is prominently implicated in studies of neuropsychiatric symptomology in non-HIV samples. Hence, this preliminary study examined: 1) the combined effects of HIV and high ELS on amygdala activity, and 2) the relation between amygdala activity and neuropsychiatric symptoms in HIV+ adults. We included 28 HIV+ adults and 25 demographically-matched HIV-negative control (HC) adults. ELS exposure was quantified using a retrospective ELS questionnaire, which defined four groups: HIV+ Low-ELS (N = 15); ...
Current treatment options for posttraumatic stress disorder (PTSD) offer modest benefits, undersc... more Current treatment options for posttraumatic stress disorder (PTSD) offer modest benefits, underscoring the need for new treatments. Repetitive transcranial magnetic stimulation (rTMS) depolarizes neurons in a targeted brain region with magnetic fields typically pulsed at low (1 Hz) or high (10 Hz) frequency to relieve major depressive disorder (MDD). Prior work suggests an intermediate pulse frequency, 5 Hz, is also efficacious for treating comorbid depressive and anxiety symptoms. In this chart review study, we systematically examined the clinical and safety outcomes in 10 patients with comorbid MDD and PTSD syndromes who received 5-Hz rTMS therapy at the Providence VA Medical Center Neuromodulation Clinic. Self-report scales measured illness severity prior to treatment, after every 5 treatments, and upon completion of treatment. Results showed significant reduction in symptoms of PTSD (p = .003, effect size = 1.12, 8/10 with reliable change) and MDD (p = .005, effect size = 1.09, 6/10 with reliable change). Stimulation was well tolerated and there were no serious adverse events. These data indicate 5-Hz rTMS may be a useful option to treat these comorbid disorders. Larger, controlled trials are needed to confirm the benefits of 5-Hz protocols observed in this pilot study.
Background: Repetitive transcranial magnetic stimulation (rTMS) to left prefrontal cortex at 10 H... more Background: Repetitive transcranial magnetic stimulation (rTMS) to left prefrontal cortex at 10 Hz is the most commonly utilized protocol for major depressive disorder (MDD). Published data suggests that left sided 5 Hz rTMS may be efficacious and well tolerated. Objective: We analyzed outcomes in a naturalistic cohort of MDD patients who could not tolerate 10 Hz rTMS and were routinely switched to 5 Hz. We hypothesized that the efficacy of 5 Hz rTMS would be equivalent to 10 Hz. Methods: Records were reviewed for patients (n ¼ 98) who received 15 or more acute rTMS treatments. The sample was split based upon the frequency (10 or 5 Hz) at which the majority of treatments were delivered. The Inventory of Depressive Symptoms (IDS-SR) and 9-Item Patient Health Questionnaire (PHQ-9) were used to evaluate outcomes. Results: Baseline IDS-SR was higher in the 5 Hz (n ¼27) than in the 10 Hz (n ¼71) group (p o.05), as was frequency of comorbid anxiety (p¼ .002). Depression outcomes did not differ between groups, and there were no differences in response or remission rates (all p4.1). Statistical power was sufficient to detect small group differences (d ¼.26). Limitations: Open-label data in a naturalistic setting. Conclusion: Outcomes associated with 5 Hz rTMS did not differ from 10 Hz, despite higher baseline depressive symptom severity and anxiety in 5 Hz patients. 5 Hz stimulation may be an alternative treatment option for patients unable to tolerate 10 Hz rTMS.
Background / Purpose: We evaluated resting state default network connectivity in subjects with ea... more Background / Purpose: We evaluated resting state default network connectivity in subjects with early life stress in the absence of medical or psychiatric illness or medication. Main conclusion: Decreased posterior cingulate cortex (PCC) to medial prefrontal cortex (MPFC) connectivity, and PCC to inferior temporal cortex connectivity, were found.
This study was designed to quantify adjunctive antidepressant use in bipolar depression and inves... more This study was designed to quantify adjunctive antidepressant use in bipolar depression and investigate whether the use of adjunctive antidepressants or presence of comorbid anxiety impacted the rate of psychiatric rehospitalization.
Background / Purpose: This study hypothesized that subjects with early life stress (ELS) would ha... more Background / Purpose: This study hypothesized that subjects with early life stress (ELS) would have changes in default network (DN) activity during working memory tasks. Previous literature has demonstrated changes in DN activity in subjects with post-traumatic stress disorder (PTSD) as well as many other psychiatric illnesses. However, there have been no studies examining the effects of ELS.We investigated DN activity in 19 subjects (10 with ELS, 9 without) to assess DN activity in the absence of other psychiatric conditions or medications. These were participants gathered from the healthy controls population of a prior completed study. Main conclusion: We found that subjects with ELS had significantly greater DN deactivation in response to cognitive challenges, compared to controls. Since ELS is highly prevalent, and not consistently assessed in imaging studies of healthy individuals, our results imply that vigorous screening is needed. We also found clear group differences that s...
Epigenetic modifications to the genome are a key mechanism involved in the biological encoding of... more Epigenetic modifications to the genome are a key mechanism involved in the biological encoding of experience. Animal studies and a growing body of literature in humans have shown that early adversity is linked to methylation of the gene for the glucocorticoid receptor (GR), which is a key regulator of the hypothalamic-pituitary-adrenal axis as well as a broad range of physiological systems including metabolic and immune function. One hundred eighty-four families participated, including n = 74 with child welfare documentation of moderate-severe maltreatment in the past 6 months. Children ranged in age from 3 to 5 years, and were racially and ethnically diverse. Structured record review and interviews in the home were used to assess a history of maltreatment, other traumas, and contextual life stressors, and a composite variable assessed the number exposures to these adversities. Methylation of regions 1D, 1F, and 1H of the GR gene was measured via sodium bisulfite pyrosequencing. The composite measure of adversity was positively correlated with methylation at exons 1D and 1F in the promoter of the GR gene. Individual stress measures were significantly associated with a several CpG sites in these regions. GR gene methylation may be a mechanism of the biobehavioral effects of adverse exposures in young children.
Cellular aging plays a role in longevity and senescence, and has been implicated in medical and p... more Cellular aging plays a role in longevity and senescence, and has been implicated in medical and psychiatric conditions, including heart disease, cancer, major depression and posttraumatic stress disorder. Telomere shortening and mitochondrial dysfunction are thought to be central to the cellular aging process. The present study examined the association between mitochondrial DNA (mtDNA) copy number and telomere length in a sample of medically healthy adults. Participants (total n=392) were divided into 4 groups based on the presence or absence of early life adversity and lifetime psychopathology: No Adversity/No Disorder, n=136; Adversity/No Disorder, n=91; No Adversity/Disorder, n=46; Adversity/Disorder, n=119. Telomere length and mtDNA copy number were measured using quantitative polymerase chain reaction. There was a positive correlation between mtDNA and telomere length in the entire sample (r=0.120, p<0.001) and in each of the four groups of participants (No Adversity/No Diso...
Telomeres are structures of tandem TTAGGG repeats that are found at the ends of chromosomes and p... more Telomeres are structures of tandem TTAGGG repeats that are found at the ends of chromosomes and preserve genomic DNA by serving as a disposable buffer to protect DNA termini during chromosome replication. In this process, the telomere itself shortens with each cell division and can consequently be thought of as a cellular 'clock', reflecting the age of a cell and the time until senescence. Telomere shortening and changes in the levels of telomerase, the enzyme that maintains telomeres, occur in the context of certain somatic diseases and in response to selected physical stressors. Emerging evidence indicates that telomeres shorten with exposure to psychosocial stress (including early-life stress) and perhaps in association with some psychiatric disorders. These discoveries suggest that telomere shortening might be a useful biomarker for the overall stress response of an organism to various pathogenic conditions. In this regard, telomeres and their response to both somatic an...
Previous research suggests that a history of early life stress (ELS) impacts working memory (WM) ... more Previous research suggests that a history of early life stress (ELS) impacts working memory (WM) in adulthood. Despite the widespread use of WM paradigms, few studies have evaluated whether ELS exposure, in the absence of psychiatric illness, also impacts WM-associated brain activity in ways that might improve sensitivity to these ELS effects or provide insights into the mechanisms of these effects. This study evaluated whether ELS affects WM behavioral performance and task-associated activity by acquiring 3T functional images from 27 medication-free healthy adults (14 with ELS) during an N-back WM task that included 0- and 2-back components. Whole brain voxel-wise analysis was performed to evaluate WM activation, followed by region of interest analyses to evaluate relationships between activation and clinical variables. ELS was associated with poorer accuracy during the 2-back (79 % ± 19 vs. 92 % ± 9, p = 0.049); accuracy and response time otherwise did not differ between groups. D...
Annals of clinical psychiatry : official journal of the American Academy of Clinical Psychiatrists, 2014
This study was designed to quantify adjunctive antidepressant use in bipolar depression and inves... more This study was designed to quantify adjunctive antidepressant use in bipolar depression and investigate whether the use of adjunctive antidepressants or presence of comorbid anxiety impacted the rate of psychiatric rehospitalization. Charts were reviewed for 377 adult patients with bipolar I depression discharged from Butler Hospital, a nonprofit psychiatric hospital in Providence, Rhode Island, from January 2008 to July 2011. Primary outcomes were impact of antidepressant exposure on readmission rates and time to readmission in the year post-discharge. Secondary analyses examined outcomes associated with anxiety, antidepressant class, and affective switch. Of the 377 patients, 233 (61.8%) were prescribed an antidepressant at discharge and 144 (38.2%) were not. Only serotonin-norepinephrine reuptake inhibitor (SNRI) exposure, compared with nonexposure, was associated with greater readmission (74.4% vs 56.7%, P = .008) and shorter time to readmission (165 ± 145 vs 210 ± 153 days, P =...
Neurostimulation is rapidly emerging as an important treatment modality for psychiatric disorders... more Neurostimulation is rapidly emerging as an important treatment modality for psychiatric disorders. One of the fastest-growing and least-regulated approaches to noninvasive therapeutic stimulation involves the application of weak electrical currents. Widespread enthusiasm for low-intensity transcranial electrical current stimulation (tCS) is reflected by the recent surge in direct-to-consumer device marketing, do-it-yourself enthusiasm, and an escalating number of clinical trials. In the wake of this rapid growth, clinicians may lack sufficient information about tCS to inform their clinical practices. Interpretation of tCS clinical trial data is aided by familiarity with basic neurophysiological principles, potential mechanisms of action of tCS, and the complicated regulatory history governing tCS devices. A growing literature includes randomized controlled trials of tCS for major depression, schizophrenia, cognitive disorders, and substance use disorders. The relative ease of use an...
Major depression is a common and debilitating illness. Over recent years, new pharmacologic treat... more Major depression is a common and debilitating illness. Over recent years, new pharmacologic treatments have been approved for this disorder, including the atypical antipsychotics. One of the benefits of these medications is their significant efficacy as augmenting agents for unipolar, nonpsychotic major depressive disorder (MDD).Aripiprazole (marketed as Abilify, Bristol-Myers Squibb/ Otsuka Pharmaceuticals) was the first medication of this class approved for adjunctive treatment of MDD, and is the 5th most commonly prescribed medication in the United States in 2010. However, despite the frequency of its use, little has been described regarding events surrounding aripiprazole discontinuation. Here I describe what is, to my knowledge, the first reported case of an aripiprazole discontinuation syndrome. While directly relevant to psychiatrists and behavioral specialists, the symptoms described here are pertinent for internists and neurologists who may encounter this medication in thei...
Academic psychiatry : the journal of the American Association of Directors of Psychiatric Residency Training and the Association for Academic Psychiatry, Jan 16, 2016
Early life stress (ELS) is an established risk factor for psychiatric illness and is associated w... more Early life stress (ELS) is an established risk factor for psychiatric illness and is associated with altered functional connectivity within- and between intrinsic neural networks. The widespread nature of these disruptions suggests that broad imaging measures of neural connectivity, such as global based connectivity (GBC), may be particularly appropriate for studies of this population. GBC is designed to identify brain regions having maximal functional connectedness with the rest of the brain, and alterations in GBC may reflect a restriction or broadening of network synchronization. We evaluated whether ELS severity predicted GBC in a sample (N = 46) with a spectrum of ELS exposure. Participants included healthy controls without ELS, those with at least moderate ELS but without psychiatric disorders, and a group of patients with ELS- related psychiatric disorders. The spatial distribution of GBC peaked in regions of the salience and default mode networks, and ELS severity predicted ...
Relative to HIV-negative adults, HIV+ adults report elevated levels of early life stress (ELS). I... more Relative to HIV-negative adults, HIV+ adults report elevated levels of early life stress (ELS). In non-HIV samples, high ELS has been linked to abnormalities in brain structure and function, as well as increased risk of neuropsychiatric symptoms. Yet, little is known about the neural effects of high ELS, and their relation to elevated neuropsychiatric symptoms, in HIV+ adults. Recent studies have revealed combined effects of HIV and high ELS on amygdala morphometry. Aberrant amygdala activity is prominently implicated in studies of neuropsychiatric symptomology in non-HIV samples. Hence, this preliminary study examined: 1) the combined effects of HIV and high ELS on amygdala activity, and 2) the relation between amygdala activity and neuropsychiatric symptoms in HIV+ adults. We included 28 HIV+ adults and 25 demographically-matched HIV-negative control (HC) adults. ELS exposure was quantified using a retrospective ELS questionnaire, which defined four groups: HIV+ Low-ELS (N = 15); ...
Current treatment options for posttraumatic stress disorder (PTSD) offer modest benefits, undersc... more Current treatment options for posttraumatic stress disorder (PTSD) offer modest benefits, underscoring the need for new treatments. Repetitive transcranial magnetic stimulation (rTMS) depolarizes neurons in a targeted brain region with magnetic fields typically pulsed at low (1 Hz) or high (10 Hz) frequency to relieve major depressive disorder (MDD). Prior work suggests an intermediate pulse frequency, 5 Hz, is also efficacious for treating comorbid depressive and anxiety symptoms. In this chart review study, we systematically examined the clinical and safety outcomes in 10 patients with comorbid MDD and PTSD syndromes who received 5-Hz rTMS therapy at the Providence VA Medical Center Neuromodulation Clinic. Self-report scales measured illness severity prior to treatment, after every 5 treatments, and upon completion of treatment. Results showed significant reduction in symptoms of PTSD (p = .003, effect size = 1.12, 8/10 with reliable change) and MDD (p = .005, effect size = 1.09, 6/10 with reliable change). Stimulation was well tolerated and there were no serious adverse events. These data indicate 5-Hz rTMS may be a useful option to treat these comorbid disorders. Larger, controlled trials are needed to confirm the benefits of 5-Hz protocols observed in this pilot study.
Background: Repetitive transcranial magnetic stimulation (rTMS) to left prefrontal cortex at 10 H... more Background: Repetitive transcranial magnetic stimulation (rTMS) to left prefrontal cortex at 10 Hz is the most commonly utilized protocol for major depressive disorder (MDD). Published data suggests that left sided 5 Hz rTMS may be efficacious and well tolerated. Objective: We analyzed outcomes in a naturalistic cohort of MDD patients who could not tolerate 10 Hz rTMS and were routinely switched to 5 Hz. We hypothesized that the efficacy of 5 Hz rTMS would be equivalent to 10 Hz. Methods: Records were reviewed for patients (n ¼ 98) who received 15 or more acute rTMS treatments. The sample was split based upon the frequency (10 or 5 Hz) at which the majority of treatments were delivered. The Inventory of Depressive Symptoms (IDS-SR) and 9-Item Patient Health Questionnaire (PHQ-9) were used to evaluate outcomes. Results: Baseline IDS-SR was higher in the 5 Hz (n ¼27) than in the 10 Hz (n ¼71) group (p o.05), as was frequency of comorbid anxiety (p¼ .002). Depression outcomes did not differ between groups, and there were no differences in response or remission rates (all p4.1). Statistical power was sufficient to detect small group differences (d ¼.26). Limitations: Open-label data in a naturalistic setting. Conclusion: Outcomes associated with 5 Hz rTMS did not differ from 10 Hz, despite higher baseline depressive symptom severity and anxiety in 5 Hz patients. 5 Hz stimulation may be an alternative treatment option for patients unable to tolerate 10 Hz rTMS.
Background / Purpose: We evaluated resting state default network connectivity in subjects with ea... more Background / Purpose: We evaluated resting state default network connectivity in subjects with early life stress in the absence of medical or psychiatric illness or medication. Main conclusion: Decreased posterior cingulate cortex (PCC) to medial prefrontal cortex (MPFC) connectivity, and PCC to inferior temporal cortex connectivity, were found.
This study was designed to quantify adjunctive antidepressant use in bipolar depression and inves... more This study was designed to quantify adjunctive antidepressant use in bipolar depression and investigate whether the use of adjunctive antidepressants or presence of comorbid anxiety impacted the rate of psychiatric rehospitalization.
Background / Purpose: This study hypothesized that subjects with early life stress (ELS) would ha... more Background / Purpose: This study hypothesized that subjects with early life stress (ELS) would have changes in default network (DN) activity during working memory tasks. Previous literature has demonstrated changes in DN activity in subjects with post-traumatic stress disorder (PTSD) as well as many other psychiatric illnesses. However, there have been no studies examining the effects of ELS.We investigated DN activity in 19 subjects (10 with ELS, 9 without) to assess DN activity in the absence of other psychiatric conditions or medications. These were participants gathered from the healthy controls population of a prior completed study. Main conclusion: We found that subjects with ELS had significantly greater DN deactivation in response to cognitive challenges, compared to controls. Since ELS is highly prevalent, and not consistently assessed in imaging studies of healthy individuals, our results imply that vigorous screening is needed. We also found clear group differences that s...
Epigenetic modifications to the genome are a key mechanism involved in the biological encoding of... more Epigenetic modifications to the genome are a key mechanism involved in the biological encoding of experience. Animal studies and a growing body of literature in humans have shown that early adversity is linked to methylation of the gene for the glucocorticoid receptor (GR), which is a key regulator of the hypothalamic-pituitary-adrenal axis as well as a broad range of physiological systems including metabolic and immune function. One hundred eighty-four families participated, including n = 74 with child welfare documentation of moderate-severe maltreatment in the past 6 months. Children ranged in age from 3 to 5 years, and were racially and ethnically diverse. Structured record review and interviews in the home were used to assess a history of maltreatment, other traumas, and contextual life stressors, and a composite variable assessed the number exposures to these adversities. Methylation of regions 1D, 1F, and 1H of the GR gene was measured via sodium bisulfite pyrosequencing. The composite measure of adversity was positively correlated with methylation at exons 1D and 1F in the promoter of the GR gene. Individual stress measures were significantly associated with a several CpG sites in these regions. GR gene methylation may be a mechanism of the biobehavioral effects of adverse exposures in young children.
Cellular aging plays a role in longevity and senescence, and has been implicated in medical and p... more Cellular aging plays a role in longevity and senescence, and has been implicated in medical and psychiatric conditions, including heart disease, cancer, major depression and posttraumatic stress disorder. Telomere shortening and mitochondrial dysfunction are thought to be central to the cellular aging process. The present study examined the association between mitochondrial DNA (mtDNA) copy number and telomere length in a sample of medically healthy adults. Participants (total n=392) were divided into 4 groups based on the presence or absence of early life adversity and lifetime psychopathology: No Adversity/No Disorder, n=136; Adversity/No Disorder, n=91; No Adversity/Disorder, n=46; Adversity/Disorder, n=119. Telomere length and mtDNA copy number were measured using quantitative polymerase chain reaction. There was a positive correlation between mtDNA and telomere length in the entire sample (r=0.120, p<0.001) and in each of the four groups of participants (No Adversity/No Diso...
Telomeres are structures of tandem TTAGGG repeats that are found at the ends of chromosomes and p... more Telomeres are structures of tandem TTAGGG repeats that are found at the ends of chromosomes and preserve genomic DNA by serving as a disposable buffer to protect DNA termini during chromosome replication. In this process, the telomere itself shortens with each cell division and can consequently be thought of as a cellular 'clock', reflecting the age of a cell and the time until senescence. Telomere shortening and changes in the levels of telomerase, the enzyme that maintains telomeres, occur in the context of certain somatic diseases and in response to selected physical stressors. Emerging evidence indicates that telomeres shorten with exposure to psychosocial stress (including early-life stress) and perhaps in association with some psychiatric disorders. These discoveries suggest that telomere shortening might be a useful biomarker for the overall stress response of an organism to various pathogenic conditions. In this regard, telomeres and their response to both somatic an...
Previous research suggests that a history of early life stress (ELS) impacts working memory (WM) ... more Previous research suggests that a history of early life stress (ELS) impacts working memory (WM) in adulthood. Despite the widespread use of WM paradigms, few studies have evaluated whether ELS exposure, in the absence of psychiatric illness, also impacts WM-associated brain activity in ways that might improve sensitivity to these ELS effects or provide insights into the mechanisms of these effects. This study evaluated whether ELS affects WM behavioral performance and task-associated activity by acquiring 3T functional images from 27 medication-free healthy adults (14 with ELS) during an N-back WM task that included 0- and 2-back components. Whole brain voxel-wise analysis was performed to evaluate WM activation, followed by region of interest analyses to evaluate relationships between activation and clinical variables. ELS was associated with poorer accuracy during the 2-back (79 % ± 19 vs. 92 % ± 9, p = 0.049); accuracy and response time otherwise did not differ between groups. D...
Annals of clinical psychiatry : official journal of the American Academy of Clinical Psychiatrists, 2014
This study was designed to quantify adjunctive antidepressant use in bipolar depression and inves... more This study was designed to quantify adjunctive antidepressant use in bipolar depression and investigate whether the use of adjunctive antidepressants or presence of comorbid anxiety impacted the rate of psychiatric rehospitalization. Charts were reviewed for 377 adult patients with bipolar I depression discharged from Butler Hospital, a nonprofit psychiatric hospital in Providence, Rhode Island, from January 2008 to July 2011. Primary outcomes were impact of antidepressant exposure on readmission rates and time to readmission in the year post-discharge. Secondary analyses examined outcomes associated with anxiety, antidepressant class, and affective switch. Of the 377 patients, 233 (61.8%) were prescribed an antidepressant at discharge and 144 (38.2%) were not. Only serotonin-norepinephrine reuptake inhibitor (SNRI) exposure, compared with nonexposure, was associated with greater readmission (74.4% vs 56.7%, P = .008) and shorter time to readmission (165 ± 145 vs 210 ± 153 days, P =...
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