Mustafa Husain | University of Texas Southwestern Medical Center at Dallas (original) (raw)

Papers by Mustafa Husain

The American Journal of Geriatric Psychiatry, 2021

Biological Psychiatry, 2017

Background: Mood disorders can be considered as imbalances in the activity of specific neuronal c... more Background: Mood disorders can be considered as imbalances in the activity of specific neuronal circuits. The alpha-amino-3-hydroxyl-5-methyl-4-isoxazolepropionic acid (AMPA) subtype of ionotropic glutamate receptors mediates the majority of fast synaptic transmission within the mammalian brain. The ubiquitous expression of the primary subunits of AMPA receptors (AMPARs), and the lack of pharmacological selectivity amongst them, preclude regional or neuronal subtype specificity. In vivo, AMPARs comprise a variety of accessory proteins. Of particular interest, TARP-gamma8 is highly expressed in the hippocampus, part of the limbic circuitry that putatively is overactive in recurrent mood disorders. Methods: We used high-throughput screening to discover compounds that selectively modulate AMPARs containing TARP-gamma8. Subsequent medicinal chemistry efforts were used to improve potency and pharmacokinetics of the hits. Assays were developed to measure target occupancy and functional effects of the compounds in vivo. Results: These compounds possess a novel mechanism-ofaction consistent with a partial attenuation of the interaction between the TARP and the pore-forming subunits of the channel. Lead molecules with oral bioavailability and high brain penetration allowed demonstration of a strong relationship between pharmacokinetics and pharmacodynamics. The compounds show anticonvulsant and anxiolytic profiles in rodent. Molecules in this class provide large safety margins relative to non-specific AMPAR inhibitors due to the improved regional specificity of TARP-gamma8 modulators. Conclusions: AMPAR modulators selective for TARP-gamma8 have the potential to be novel treatments for anxiety/depression, bipolar disorder, temporal lobe epilepsy, and/or prodromal schizophrenia. This project also represents proof-of-concept for pharmacological targeting of accessory proteins and smallmolecule modulation of protein-protein interactions.

Current Behavioral Neuroscience Reports, 2016

Purpose of Review Treatment-resistant depression (TRD) affects a significant subset of depressed ... more Purpose of Review Treatment-resistant depression (TRD) affects a significant subset of depressed patients. It is estimated that about 30 % of patients with major depressive disorder do not respond to standard treatments. For these patients, electroconvulsive therapy (ECT) remains the most effective treatment despite being limited by its side effects. Modifications to ECT parameters have suggested that it may be possible to separate the therapeutic effects of convulsive therapy from the production of side effects. Recent Findings Magnetic seizure therapy (MST), which uses electromagnetic induction to induce a seizure, is an alternative, experimental convulsive treatment for major depression. Seizures induced by MST are more focal than those produced by ECT, thereby offering greater control over the induced electric field. Most importantly, it offers the potential to provide antidepressant effect without cognitive side effects. Recent findings have further shown the effectiveness of MST and compared cognitive and metabolic side effects to ECT. Summary This article reviews the current literature for clinical studies on MST. While initial results are promising, future work is needed to compare MST efficacy with other antidepressant treatments.

American Journal of Psychiatry, 2021

The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry, 2018

Contemporary Clinical Trials, 2018

Symptoms of agitation, aggression, and psychosis frequently occur in patients with Alzheimer's di... more Symptoms of agitation, aggression, and psychosis frequently occur in patients with Alzheimer's disease (AD). These symptoms are distressing to patients and caregivers, often lead to institutionalization, are associated with increased mortality, and are very difficult to treat. Lithium is an established treatment for bipolar and other psychotic disorders in which agitation can occur.

The journal of ECT, Jan 16, 2016

Electroconvulsive therapy (ECT) remains an effective treatment for major depressive disorder. Sin... more Electroconvulsive therapy (ECT) remains an effective treatment for major depressive disorder. Since 1995, Texas has maintained an ECT database including patient diagnoses and outcomes, and reporting any deaths within 14 days of receiving an ECT treatment, encompassing a total of 166,711 ECT treatments administered in Texas over the previously unreported period of 1998 to 2013. Descriptive analysis summarized information on deaths reported during the 16-year period-cause of death, type of treatment (index or maintenance) and patient demographics. Multiple logistic regression of death incidence by treatment session was performed to determine whether patient age, sex, race, diagnosis, or year of treatment was associated with death after ECT. Of those deaths occurring within 1 day of an ECT treatment, the death rate was 2.4 per 100,000 treatments. Looking at all deaths within 14 days of an ECT treatment, the death rate increased to 18 per 100,000 treatments but included all deaths regar...

AJNR. American journal of neuroradiology

Intermediate T2-weighted MR images and a systematic sampling stereological method were used in 37... more Intermediate T2-weighted MR images and a systematic sampling stereological method were used in 37 normal volunteers, 24 to 79 years old, to assess the effects of age and sex on cerebellar volume. Female subjects (n = 21) had significantly smaller cerebellar volumes compared with males (n = 16) of similar age (t = -3.9, p less than .0008, two-tail t test). Using straight-line, univariate regression, we determined that age was not a significant predictor of cerebellar volume (R2 = 0.07, t = -1.66, p = 0.11), whereas gender did appear to account for a significant amount of variability in cerebellar volume (R2 = 0.33, t = -4.13, p = .0002). The mean absolute cerebellar volume in this study was 112 ml (SD +/- 16) for all subjects, 104 ml (SD +/- 10) for females, and 122 ml (SD +/- 16) for males. This study demonstrates the feasibility of using MR images along with a systematic stereological method to assess in vivo human cerebellar volume, thereby providing a research tool to correlate c...

European Archives of Psychiatry and Clinical Neuroscience, 2019

Recent genome-wide association studies have demonstrated that the genetic burden associated with ... more Recent genome-wide association studies have demonstrated that the genetic burden associated with depression correlates with depression severity. Therefore, conducting genetic studies of patients at the most severe end of the depressive disorder spectrum, those with treatment-resistant depression and who are prescribed electroconvulsive therapy (ECT), could lead to a better understanding of the genetic underpinnings of depression. Despite ECT being one of the most effective forms of treatment for severe depressive disorders, it is usually placed at the end of treatment algorithms of current guidelines. This is perhaps because ECT has controlled risk and logistical demands including use of general anaesthesia and muscle relaxants and side-effects such as short-term memory impairment. Better understanding of the genetics and biology of ECT response and of cognitive side-effects could lead to more personalized treatment decisions. To enhance the understanding of the genomics of severe depression and ECT response, researchers and ECT providers from around the world and from various depression or ECT networks, but not limited to, such as the Psychiatric Genomics Consortium, the Clinical Alliance and Research in ECT, and the National Network of Depression Centers have formed the Genetics of ECT International Consortium (Gen-ECT-ic). Gen-ECT-ic will organize the largest clinical and genetic collection to date to study the genomics of severe depressive disorders and response to ECT, aiming for 30,000 patients worldwide using a GWAS approach. At this stage it will be the largest genomic study on treatment response in depression. Retrospective data abstraction and prospective data collection will be facilitated by a uniform data collection approach that is flexible and will incorporate data from many clinical practices. Gen-ECT-ic invites all ECT providers and researchers to join its efforts.

The American journal of psychiatry, Apr 1, 2017

The journal of ECT, 2007

The use of double-blind designs, normally the criterion standard of clinical trials, is impossibl... more The use of double-blind designs, normally the criterion standard of clinical trials, is impossible when comparing medication therapy to procedural therapies for depression. In the Consortium for Research in Electroconvulsive Therapy (CORE) trial, depressed patients recently remitted with electroconvulsive therapy (ECT) were randomly assigned to receive continuation therapy with either ECT or medications. The purpose of this article is to describe the design characteristics and challenges of the trial and of our method of dealing with the lack of double-blind outcome assessment. The primary outcome measure was time to relapse of depression in the continuation phase. We developed a method to achieve partial blinding of depressive severity assessment. This consisted of videotaping the structured interviews, having the video tapes co-rated by personnel not involved in the patient's care, and a videotape-tracking maneuver so that the assessor of the videotapes could be blinded to pha...

The Journal of ECT, 2009

Objective-We sought to examine the relationship of seizure threshold (ST) to age and other demogr... more Objective-We sought to examine the relationship of seizure threshold (ST) to age and other demographic characteristics in a large sample where ST was determined by the dose titration (DT) method. We also compared the resulting stimulation levels to estimates predicted by an age-based formula, the half-age (HA) method. Methods-In a multicenter prospective study patients received a standardized course of bilateral ECT for major depression using a brief pulse device. The ST was determined at the first treatment using a fixed algorithm of stimulations. Subsequent seizures were induced at a level 50% higher than the empirically determined ST. We only included data from subject receiving methohexital anesthesia. We correlated ST with demographic and clinical characteristics of the sample. The actual dosing levels at the second treatment were compared to estimates based on HA. Results-Of the original 531 subjects, 402 met criteria for the current analysis. The ST was positively correlated with age. Male patients had slightly higher ST than female patients. Neither race, severity of illness, psychosis, nor use of psychotropic medications affected ST. Little variability in titrated ST was observed among our patients. An ST of 40 ("percent of charge") or lower was found in 97.5% of patients, with either 20 or 40 in 80% of patients. Ninety-six percent of the patients were treated at the three levels of 15%, 30% or 60%. Estimated HA stimulus levels offered a wider range of choices compared to this particular algorithm used for ST determination at an average level of 18% above the determined ST. Conclusions-ST correlates strongly with age, while there is weaker relation between ST and sex. There was little individual variation of ST determined by DT method among subjects, possibly because of the wide spacing between steps of this particular titration algorithm. HA estimates were 18% above the empirically determined ST. This suggests that the use of the HA estimates at the first treatment may result in fewer stimulations compared to the DT method.

Psychiatry Research, 2004

Patients treated with electroconvulsive therapy (ECT) were divided into those with less severe de... more Patients treated with electroconvulsive therapy (ECT) were divided into those with less severe depression and those with more severe depression. In the less severely depressed group, high somatic anxiety and hypochondriasis predicted a low likelihood of sustained remission with ECT. In the more severely depressed group, these traits were not predictive of ECT outcome.

Biological Psychiatry, 2000

father, mother, and siblings did not differ in their family assessment from their counterparts in... more father, mother, and siblings did not differ in their family assessment from their counterparts in healthy families. Anorectic restricting patients rated their mother (p Ͻ .05), and the father rated the siblings (p Ͻ .04) as better functioning than healthy families did. Bulimic patients with AN rated themselves as more disturbed than restricting AN patients (p Ͻ .002) or healthy adolescents (p Ͻ .002). Families of bulimic AN patients rated five relationships on the dyadic scale as more dysfunctioning than restricting AN patients: daughter rating father (p Ͻ .007) and mother (p Ͻ .008), father rating daughter (Ͻ.03), siblings (p.02) and mother rating siblings (Ͻ.05). The findings suggest specific family-wide patterns of functioning differentiating both types of AN. They confirm a higher degree of dissatisfaction and problematic relationships in AN families than in healthy families.

The Journal of ECT, 2008

The seizure threshold (ST) is a measure of the minimum electrical energy necessary to induce a gr... more The seizure threshold (ST) is a measure of the minimum electrical energy necessary to induce a grand mal seizure. Dose titration of the ST has been suggested to optimize stimulus dosing in electroconvulsive therapy (ECT). The change in ST with remission is examined in a large sample of unipolar depressed patients. Methods: In a study of continuation treatments after successful ECT, the ST was determined at the first treatment and again 1 week after remission using a conventional ST measurement protocol. Patients were treated with bilateral electrode placement at 150% above the measured ST. Results: In 80 subjects, the ST measured the same in 70%, increased in 21%, and decreased in 9% at remission. Conclusions: In a study of bilateral ECT, the ST did not rise conclusively with remission.

The Journal of ECT, 2008

Objectives-Effective strategies to prolong remission post ECT are urgently needed. Fixed schedule... more Objectives-Effective strategies to prolong remission post ECT are urgently needed. Fixed schedules for continuation ECT cannot adapt to early signs of impending relapse. Symptom-Titrated, Algorithm-Based Longitudinal ECT (STABLE) is proposed as a novel patient-focused approach to individualize the ECT schedule. In STABLE, the ECT schedule adapts to symptom fluctuations to prevent over-treatment of those who do not need it, and to recapture response in those who might have otherwise relapsed with a rigid dosing schedule. Here we back-test STABLE to optimize the algorithm for subsequent testing in a prospective trial. Methods-Three variations of the STABLE algorithm, differing in cutoff points to trigger or withhold additional ECT, were back-tested in a dataset of 89 patients randomized to the C-ECT arm in the CORE study comparing C-ECT with combination pharmacotherapy. Results-The selected algorithm identified 100% of patients who ultimately relapsed as requiring additional ECT at an average of 2.2 weeks prior to relapse, while exposing 20% of sustained remitters to additional ECT. Other variations either failed to capture impending relapse, or exposed an unacceptably large percentage of patients to potentially unnecessary ECT. Conclusions-This patient-focused approach to relapse prevention is an attempt to provide the first operationalized guidance to the field regarding how to conduct continuation ECT. The effectiveness of this approach should be tested in a randomized controlled trial.

The British journal of psychiatry : the journal of mental science, 2015

The American Journal of Geriatric Psychiatry, 2021

Biological Psychiatry, 2017

Background: Mood disorders can be considered as imbalances in the activity of specific neuronal c... more Background: Mood disorders can be considered as imbalances in the activity of specific neuronal circuits. The alpha-amino-3-hydroxyl-5-methyl-4-isoxazolepropionic acid (AMPA) subtype of ionotropic glutamate receptors mediates the majority of fast synaptic transmission within the mammalian brain. The ubiquitous expression of the primary subunits of AMPA receptors (AMPARs), and the lack of pharmacological selectivity amongst them, preclude regional or neuronal subtype specificity. In vivo, AMPARs comprise a variety of accessory proteins. Of particular interest, TARP-gamma8 is highly expressed in the hippocampus, part of the limbic circuitry that putatively is overactive in recurrent mood disorders. Methods: We used high-throughput screening to discover compounds that selectively modulate AMPARs containing TARP-gamma8. Subsequent medicinal chemistry efforts were used to improve potency and pharmacokinetics of the hits. Assays were developed to measure target occupancy and functional effects of the compounds in vivo. Results: These compounds possess a novel mechanism-ofaction consistent with a partial attenuation of the interaction between the TARP and the pore-forming subunits of the channel. Lead molecules with oral bioavailability and high brain penetration allowed demonstration of a strong relationship between pharmacokinetics and pharmacodynamics. The compounds show anticonvulsant and anxiolytic profiles in rodent. Molecules in this class provide large safety margins relative to non-specific AMPAR inhibitors due to the improved regional specificity of TARP-gamma8 modulators. Conclusions: AMPAR modulators selective for TARP-gamma8 have the potential to be novel treatments for anxiety/depression, bipolar disorder, temporal lobe epilepsy, and/or prodromal schizophrenia. This project also represents proof-of-concept for pharmacological targeting of accessory proteins and smallmolecule modulation of protein-protein interactions.

Current Behavioral Neuroscience Reports, 2016

Purpose of Review Treatment-resistant depression (TRD) affects a significant subset of depressed ... more Purpose of Review Treatment-resistant depression (TRD) affects a significant subset of depressed patients. It is estimated that about 30 % of patients with major depressive disorder do not respond to standard treatments. For these patients, electroconvulsive therapy (ECT) remains the most effective treatment despite being limited by its side effects. Modifications to ECT parameters have suggested that it may be possible to separate the therapeutic effects of convulsive therapy from the production of side effects. Recent Findings Magnetic seizure therapy (MST), which uses electromagnetic induction to induce a seizure, is an alternative, experimental convulsive treatment for major depression. Seizures induced by MST are more focal than those produced by ECT, thereby offering greater control over the induced electric field. Most importantly, it offers the potential to provide antidepressant effect without cognitive side effects. Recent findings have further shown the effectiveness of MST and compared cognitive and metabolic side effects to ECT. Summary This article reviews the current literature for clinical studies on MST. While initial results are promising, future work is needed to compare MST efficacy with other antidepressant treatments.

American Journal of Psychiatry, 2021

The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry, 2018

Contemporary Clinical Trials, 2018

Symptoms of agitation, aggression, and psychosis frequently occur in patients with Alzheimer's di... more Symptoms of agitation, aggression, and psychosis frequently occur in patients with Alzheimer's disease (AD). These symptoms are distressing to patients and caregivers, often lead to institutionalization, are associated with increased mortality, and are very difficult to treat. Lithium is an established treatment for bipolar and other psychotic disorders in which agitation can occur.

The journal of ECT, Jan 16, 2016

Electroconvulsive therapy (ECT) remains an effective treatment for major depressive disorder. Sin... more Electroconvulsive therapy (ECT) remains an effective treatment for major depressive disorder. Since 1995, Texas has maintained an ECT database including patient diagnoses and outcomes, and reporting any deaths within 14 days of receiving an ECT treatment, encompassing a total of 166,711 ECT treatments administered in Texas over the previously unreported period of 1998 to 2013. Descriptive analysis summarized information on deaths reported during the 16-year period-cause of death, type of treatment (index or maintenance) and patient demographics. Multiple logistic regression of death incidence by treatment session was performed to determine whether patient age, sex, race, diagnosis, or year of treatment was associated with death after ECT. Of those deaths occurring within 1 day of an ECT treatment, the death rate was 2.4 per 100,000 treatments. Looking at all deaths within 14 days of an ECT treatment, the death rate increased to 18 per 100,000 treatments but included all deaths regar...

AJNR. American journal of neuroradiology

Intermediate T2-weighted MR images and a systematic sampling stereological method were used in 37... more Intermediate T2-weighted MR images and a systematic sampling stereological method were used in 37 normal volunteers, 24 to 79 years old, to assess the effects of age and sex on cerebellar volume. Female subjects (n = 21) had significantly smaller cerebellar volumes compared with males (n = 16) of similar age (t = -3.9, p less than .0008, two-tail t test). Using straight-line, univariate regression, we determined that age was not a significant predictor of cerebellar volume (R2 = 0.07, t = -1.66, p = 0.11), whereas gender did appear to account for a significant amount of variability in cerebellar volume (R2 = 0.33, t = -4.13, p = .0002). The mean absolute cerebellar volume in this study was 112 ml (SD +/- 16) for all subjects, 104 ml (SD +/- 10) for females, and 122 ml (SD +/- 16) for males. This study demonstrates the feasibility of using MR images along with a systematic stereological method to assess in vivo human cerebellar volume, thereby providing a research tool to correlate c...

European Archives of Psychiatry and Clinical Neuroscience, 2019

Recent genome-wide association studies have demonstrated that the genetic burden associated with ... more Recent genome-wide association studies have demonstrated that the genetic burden associated with depression correlates with depression severity. Therefore, conducting genetic studies of patients at the most severe end of the depressive disorder spectrum, those with treatment-resistant depression and who are prescribed electroconvulsive therapy (ECT), could lead to a better understanding of the genetic underpinnings of depression. Despite ECT being one of the most effective forms of treatment for severe depressive disorders, it is usually placed at the end of treatment algorithms of current guidelines. This is perhaps because ECT has controlled risk and logistical demands including use of general anaesthesia and muscle relaxants and side-effects such as short-term memory impairment. Better understanding of the genetics and biology of ECT response and of cognitive side-effects could lead to more personalized treatment decisions. To enhance the understanding of the genomics of severe depression and ECT response, researchers and ECT providers from around the world and from various depression or ECT networks, but not limited to, such as the Psychiatric Genomics Consortium, the Clinical Alliance and Research in ECT, and the National Network of Depression Centers have formed the Genetics of ECT International Consortium (Gen-ECT-ic). Gen-ECT-ic will organize the largest clinical and genetic collection to date to study the genomics of severe depressive disorders and response to ECT, aiming for 30,000 patients worldwide using a GWAS approach. At this stage it will be the largest genomic study on treatment response in depression. Retrospective data abstraction and prospective data collection will be facilitated by a uniform data collection approach that is flexible and will incorporate data from many clinical practices. Gen-ECT-ic invites all ECT providers and researchers to join its efforts.

The American journal of psychiatry, Apr 1, 2017

The journal of ECT, 2007

The use of double-blind designs, normally the criterion standard of clinical trials, is impossibl... more The use of double-blind designs, normally the criterion standard of clinical trials, is impossible when comparing medication therapy to procedural therapies for depression. In the Consortium for Research in Electroconvulsive Therapy (CORE) trial, depressed patients recently remitted with electroconvulsive therapy (ECT) were randomly assigned to receive continuation therapy with either ECT or medications. The purpose of this article is to describe the design characteristics and challenges of the trial and of our method of dealing with the lack of double-blind outcome assessment. The primary outcome measure was time to relapse of depression in the continuation phase. We developed a method to achieve partial blinding of depressive severity assessment. This consisted of videotaping the structured interviews, having the video tapes co-rated by personnel not involved in the patient's care, and a videotape-tracking maneuver so that the assessor of the videotapes could be blinded to pha...

The Journal of ECT, 2009

Objective-We sought to examine the relationship of seizure threshold (ST) to age and other demogr... more Objective-We sought to examine the relationship of seizure threshold (ST) to age and other demographic characteristics in a large sample where ST was determined by the dose titration (DT) method. We also compared the resulting stimulation levels to estimates predicted by an age-based formula, the half-age (HA) method. Methods-In a multicenter prospective study patients received a standardized course of bilateral ECT for major depression using a brief pulse device. The ST was determined at the first treatment using a fixed algorithm of stimulations. Subsequent seizures were induced at a level 50% higher than the empirically determined ST. We only included data from subject receiving methohexital anesthesia. We correlated ST with demographic and clinical characteristics of the sample. The actual dosing levels at the second treatment were compared to estimates based on HA. Results-Of the original 531 subjects, 402 met criteria for the current analysis. The ST was positively correlated with age. Male patients had slightly higher ST than female patients. Neither race, severity of illness, psychosis, nor use of psychotropic medications affected ST. Little variability in titrated ST was observed among our patients. An ST of 40 ("percent of charge") or lower was found in 97.5% of patients, with either 20 or 40 in 80% of patients. Ninety-six percent of the patients were treated at the three levels of 15%, 30% or 60%. Estimated HA stimulus levels offered a wider range of choices compared to this particular algorithm used for ST determination at an average level of 18% above the determined ST. Conclusions-ST correlates strongly with age, while there is weaker relation between ST and sex. There was little individual variation of ST determined by DT method among subjects, possibly because of the wide spacing between steps of this particular titration algorithm. HA estimates were 18% above the empirically determined ST. This suggests that the use of the HA estimates at the first treatment may result in fewer stimulations compared to the DT method.

Psychiatry Research, 2004

Patients treated with electroconvulsive therapy (ECT) were divided into those with less severe de... more Patients treated with electroconvulsive therapy (ECT) were divided into those with less severe depression and those with more severe depression. In the less severely depressed group, high somatic anxiety and hypochondriasis predicted a low likelihood of sustained remission with ECT. In the more severely depressed group, these traits were not predictive of ECT outcome.

Biological Psychiatry, 2000

father, mother, and siblings did not differ in their family assessment from their counterparts in... more father, mother, and siblings did not differ in their family assessment from their counterparts in healthy families. Anorectic restricting patients rated their mother (p Ͻ .05), and the father rated the siblings (p Ͻ .04) as better functioning than healthy families did. Bulimic patients with AN rated themselves as more disturbed than restricting AN patients (p Ͻ .002) or healthy adolescents (p Ͻ .002). Families of bulimic AN patients rated five relationships on the dyadic scale as more dysfunctioning than restricting AN patients: daughter rating father (p Ͻ .007) and mother (p Ͻ .008), father rating daughter (Ͻ.03), siblings (p.02) and mother rating siblings (Ͻ.05). The findings suggest specific family-wide patterns of functioning differentiating both types of AN. They confirm a higher degree of dissatisfaction and problematic relationships in AN families than in healthy families.

The Journal of ECT, 2008

The seizure threshold (ST) is a measure of the minimum electrical energy necessary to induce a gr... more The seizure threshold (ST) is a measure of the minimum electrical energy necessary to induce a grand mal seizure. Dose titration of the ST has been suggested to optimize stimulus dosing in electroconvulsive therapy (ECT). The change in ST with remission is examined in a large sample of unipolar depressed patients. Methods: In a study of continuation treatments after successful ECT, the ST was determined at the first treatment and again 1 week after remission using a conventional ST measurement protocol. Patients were treated with bilateral electrode placement at 150% above the measured ST. Results: In 80 subjects, the ST measured the same in 70%, increased in 21%, and decreased in 9% at remission. Conclusions: In a study of bilateral ECT, the ST did not rise conclusively with remission.

The Journal of ECT, 2008

Objectives-Effective strategies to prolong remission post ECT are urgently needed. Fixed schedule... more Objectives-Effective strategies to prolong remission post ECT are urgently needed. Fixed schedules for continuation ECT cannot adapt to early signs of impending relapse. Symptom-Titrated, Algorithm-Based Longitudinal ECT (STABLE) is proposed as a novel patient-focused approach to individualize the ECT schedule. In STABLE, the ECT schedule adapts to symptom fluctuations to prevent over-treatment of those who do not need it, and to recapture response in those who might have otherwise relapsed with a rigid dosing schedule. Here we back-test STABLE to optimize the algorithm for subsequent testing in a prospective trial. Methods-Three variations of the STABLE algorithm, differing in cutoff points to trigger or withhold additional ECT, were back-tested in a dataset of 89 patients randomized to the C-ECT arm in the CORE study comparing C-ECT with combination pharmacotherapy. Results-The selected algorithm identified 100% of patients who ultimately relapsed as requiring additional ECT at an average of 2.2 weeks prior to relapse, while exposing 20% of sustained remitters to additional ECT. Other variations either failed to capture impending relapse, or exposed an unacceptably large percentage of patients to potentially unnecessary ECT. Conclusions-This patient-focused approach to relapse prevention is an attempt to provide the first operationalized guidance to the field regarding how to conduct continuation ECT. The effectiveness of this approach should be tested in a randomized controlled trial.

The British journal of psychiatry : the journal of mental science, 2015