New depression test identifies men who could be at up to 30x the risk of suicidal ideation

by South Australian Health and Medical Research Institute (SAHMRI)

Credit: Shutterstock

New research from SAHMRI, the University of Adelaide, CSIRO Australia's national science agency, Orygen and the Freemasons Center for Male Health and Well-being (FCMHW) has found men who score high on both traditional measures of depression symptoms and University of Adelaide's recently developed Short-Form Male Depression Risk Scale (MDRS-7), may be up to 30 times the risk of suicidal thinking.

31 may 2022--The study, published in BMJ Open and led by psychologist and Ph.D. candidate, Danielle Herreen, examined the effectiveness of the MDRS in identifying men at risk of depression and suicide who could be missed by mental health assessment tools currently being used by GP's to screen the condition.

"Around 10% of men with depression score below the threshold for this disorder on traditional tests but will flag high on the Male Depression Risk Scale. This represents a whole subset of men who could have been flying under the radar and can now be detected," Ms. Herreen said.

"We found some men who may have depression or who are at risk of suicide express their distress in different ways to what we typically look for. This often appears as behaviors that may be perceived as more stereotypically masculine."

The short-form MDRS consists of 7 questions to ensure timely completion and assesses men across a spectrum of 7 previously ignored domains.

The areas assessed include, aggression, anger, emotion suppression, alcohol use, drug use, somatic symptoms and risk-taking.

Standard practice has involved assessing symptoms including low mood, loss of interest in activities, appetite changes, difficulty concentrating and feelings of worthlessness. This approach fails to recognize a unique and different set of red flags pointing to underlying psychological distress in some men.

Co-author and Clinical Psychologist, Dr. Simon Rice from the University of Melbourne says the aim of the new scale isn't to replace the current approach, but to add value, allowing for a more comprehensive reading of an individual's psychological state.

"Our research shows that combining traditional screening methods with these new questions, gives a much stronger indication of a person's overall risk of depression and suicide," Dr. Rice said.

"More importantly, we have shown that the risk of suicidality can be up to 30 times higher in men who score high on both tests and it may be beneficial for GP's and other health professionals to add the Male Depression Risk Scale to their assessments of male patients."

Researchers are encouraging clinicians working in a role that involves one-on-one male mental health assessments to consider adopting the MDRS as part of their standard practice.

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More information: Danielle Herreen et al, Brief assessment of male depression in clinical care: Validation of the Male Depression Risk Scale short form in a cross-sectional study of Australian men, BMJ Open (2022). DOI: 10.1136/bmjopen-2021-053650

Journal information: BMJ Open 

Brain stimulation improves depression symptoms, restores brain waves in clinical study

by University of North Carolina Health Care

Electrode netting and custom-made technology allows the Frohlich lab at the UNC School of Medicine to stimulate specific parts of the brain in particular ways. Credit: Brian Strickland

With a weak alternating electrical current sent through electrodes attached to the scalp, UNC School of Medicine researchers successfully targeted a naturally occurring electrical pattern in a specific part of the brain and markedly improved depression symptoms in about 70 percent of participants in a clinical study.

14 mar 2019--The research, published in Translational Psychiatry, lays the groundwork for larger research studies to use a specific kind of electrical brain stimulation called transcranial alternating current stimulation (tACS) to treat people diagnosed with major depression.

"We conducted a small study of 32 people because this sort of approach had never been done before," said senior author Flavio Frohlich, Ph.D., associate professor of psychiatry and director of the Carolina Center for Neurostimulation. "Now that we've documented how this kind of tACS can reduce depression symptoms, we can fine tune our approach to help many people in a relatively inexpensive, noninvasive way."

Frohlich, who joined the UNC School of Medicine in 2011, is a leading pioneer in this field who also published the first clinical trials of tACS in schizophrenia and chronic pain.

His tACS approach is unlike the more common brain stimulation technique called transcranial direct stimulation (tDCS), which sends a steady stream of weak electricity through electrodes attached to various parts of the brain. That approach has had mixed results in treating various conditions, including depression. Frohlich's tACS paradigm is newer and has not been investigated as thoroughly as tDCS. Frohlich's approach focuses on each individual's specific alpha oscillations, which appear as waves between 8 and 12 Hertz on an electroencephalogram (EEG). The waves in this range rise in predominance when we close our eyes and daydream, meditate, or conjure ideas—essentially when our brains shut out sensory stimuli, such as what we see, feel, and hear.

Previous research showed that people with depression featured imbalanced alpha oscillations; the waves were overactive in the left frontal cortex. Frohlich thought his team could target these oscillations to bring them back in synch with the alpha oscillations in the right frontal cortex. And if Frohlich's team could achieve that, then maybe depression symptoms would be decreased.

His lab recruited 32 people diagnosed with depression and surveyed each participant before the study, according to the Montgomery-Åsberg Depression Rating Scale (MADRS), a standard measure of depression.

The participants were then separated into three groups. One group received the sham placebo stimulation—a brief electrical stimulus to mimic the sensation at the beginning of a tACS session. A control group received a 40-Hertz tACS intervention, well outside the range that the researchers thought would affect alpha oscillations. A third group received the treatment intervention—a 10-Hertz tACS electrical current that targeted each individual's naturally occurring alpha waves. Each person underwent their invention for 40 minutes on five consecutive days. None of the participants knew which group they were in, and neither did the researchers, making this a randomized double-blinded clinical study—the gold standard in biomedical research. Each participant took the MADRS immediately following the five-day regimen, at two weeks, and again at four weeks.

Prior to the study, Frohlich set the primary outcome at four weeks, meaning that the main goal of the study was to assess whether tACS could bring each individual's alpha waves back into balance and decrease symptoms of depression four weeks after the five-day intervention. He set this primary outcome because scientific literature on the study of tDCS also used the four-week mark.

Frohlich's team found that participants in the 10-Hertz tACS group featured a decrease in alpha oscillations in the left frontal cortex; they were brought back in synch with the right side of the frontal cortex. But the researchers did not find a statistically significant decrease in depression symptoms in the 10-Hertz tACS group, as opposed to the sham or control groups at four weeks.

But when Frohlich's team looked at data from two weeks after treatment, they found that 70 percent of people in the treatment group reported at least a 50 percent reduction of depression symptoms, according to their MADRS scores. This response rate was significantly higher than the one for the two other control groups. A few of the participants had such dramatic decreases that Frohlich's team is currently writing case-studies on them. Participants in the placebo and control groups experienced no such reduction in symptoms.

"It's important to note that this is a first-of-its kind study," Frohlich said. "When we started this research with computer simulations and preclinical studies, it was unclear if we would see an effect in people days after tACS treatment—let alone if tACS could become a treatment for psychiatric illnesses. It was unclear what would happen if we treated people several days in a row or what effect we might see weeks later. So, the fact that we've seen such positive results from this study gives me confidence our approach could help many people with depression."

Frohlich's lab is currently recruiting for two similar follow-up studies.

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More information: Morgan L. Alexander et al, Double-blind, randomized pilot clinical trial targeting alpha oscillations with transcranial alternating current stimulation (tACS) for the treatment of major depressive disorder (MDD), Translational Psychiatry (2019). DOI: 10.1038/s41398-019-0439-0

Provided by University of North Carolina Health Care

Low vitamin D levels linked to depression, psychiatrists report

Low levels of vitamin D have been linked to depression, according to UT Southwestern Medical Center psychiatrists working with the Cooper Center Longitudinal Study. It is believed to be the largest such investigation ever undertaken.

09 jan 2012--Low levels of vitamin D already are associated with a cavalcade of health woes from cardiovascular diseases to neurological ailments. This new study – published in Mayo Clinic Proceedings – helps clarify a debate that erupted after smaller studies produced conflicting results about the relationship between vitamin D and depression. Major depressive disorder affects nearly one in 10 adults in the U.S.

"Our findings suggest that screening for vitamin D levels in depressed patients – and perhaps screening for depression in people with low vitamin D levels – might be useful," said Dr. E. Sherwood Brown, professor of psychiatry and senior author of the study, done in conjunction with The Cooper Institute in Dallas. "But we don't have enough information yet to recommend going out and taking supplements."

UT Southwestern researchers examined the results of almost 12,600 participants from late 2006 to late 2010. Dr. Brown and colleagues from The Cooper Institute found that higher vitamin D levels were associated with a significantly decreased risk of current depression, particularly among people with a prior history of depression. Low vitamin D levels were associated with depressive symptoms, particularly those with a history of depression, so primary care patients with a history of depression may be an important target for assessing vitamin D levels. The study did not address whether increasing vitamin D levels reduced depressive symptoms.

The scientists have not determined the exact relationship – whether low vitamin D contributes to symptoms of depression, whether depression itself contributes to lower vitamin D levels, or chemically how that happens. But vitamin D may affect neurotransmitters, inflammatory markers and other factors, which could help explain the relationship with depression, said Dr. Brown, who leads the psychoneuroendocrine research program at UT Southwestern.

Vitamin D levels are now commonly tested during routine physical exams, and they already are accepted as risk factors for a number of other medical problems: autoimmune diseases; heart and vascular disease; infectious diseases; osteoporosis; obesity; diabetes; certain cancers; and neurological disorders such as Alzheimer's and Parkinson's diseases, multiple sclerosis, and general cognitive decline.

Investigators used information gathered by the institute, which has 40 years of data on runners and other fit volunteers. UT Southwestern has a partnership with the institute, a preventive medicine research and educational nonprofit located at the Cooper Aerobics Center, to develop a joint scientific medical research program aimed at improving health and preventing a wide range of chronic diseases. The institute maintains one of the world's most extensive databases – known as the Cooper Center Longitudinal Study – that includes detailed information from more than 250,000 clinic visits that has been collected since Dr. Kenneth Cooper founded the institute and clinic in 1970.

Provided by UT Southwestern Medical Center

Study identifies those elderly most at risk for major depression

University of Rochester Medical Center researchers have pinpointed the prime factors identifying which elderly persons are at the highest risk for developing major depression.

19 dec 2009--The researchers, led by Jeffrey M. Lyness, M.D., professor of Psychiatry at the Medical Center, reported their findings in an article in the December issue of The American Journal of Psychiatry.

Preventive treatments for people in the high-risk group hold promise for providing the greatest health benefit at the lowest cost, the researchers concluded.

"People with low-level depressive symptoms, who perceive that they have poor quality social support from other people, and with a past history of depression, were at particularly high risk to develop new major depression within the one-to-four year time period of the study," Lyness said. "This is good news, as we in the field are just learning how to prevent depression in particular high-risk groups. Future work will be able to test whether any of a variety of treatments—perhaps psychotherapy, perhaps medication, perhaps other things such as exercise—will help to prevent depression in persons suffering from the risks we identified in this study."

More than 600 people who were 65 years of age or older took part in the study. They were recruited from private practices and University-affiliated clinics in internal medicine, geriatrics and family medicine in Monroe County, N.Y. Only participants without an active diagnosis of major depression were included in the analyses.

Annual follow-up in-person interviews were conducted for up to four years. Information obtained from telephone contacts and annual medical chart reviews supplemented the interviews. Thirty-three participants, or about 5.3 percent, developed an episode of major depression during the study period.

In their analysis, the researchers concluded the "number needed to treat," an epidemiological measure used in determining the effectiveness of a medical intervention, was five. This means the fully effective preventive treatment of five individuals presenting the indicators would prevent one new case of major depression.

In an editorial in the journal, Warren D. Taylor, M.D., associate professor of Psychiatry at Duke University Medical Center, agreed the number needed to treat was low and indicated cost effectiveness.

"Given the complications of depression in an elderly population, a preventive approach for this at-risk population may be quite important to not only prevent psychological suffering but to also avoid the deleterious effects of depression on comorbid medical illness," Taylor wrote.

The researchers concluded "the present study may inform current clinical practice by fostering early detection and intervention critical to improving patient outcomes for depression."

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In addition to Lyness, authors of the article include: Wan Tang, Ph.D., research assistant professor of Biostatistics, Xin Tu, Ph.D., professor of Biostatistics and of Psychiatry, Yeates Conwell, M.D., professor of Psychiatry, and Qin Yu, Ph.D., research associate at the University of Pennsylvania.

Analysis Gives Venlafaxine Slender Edge Over SSRIs

By Charles Bankhead
ATLANTA, Feb. 27 -- For achieving major depression remission, a dual neurotransmitter reuptake inhibitor has a thin advantage over selective serotonin reuptake inhibitors, found a meta-analysis. Slightly more patients with major depression went into remission with venlafaxine (Effexor), the dual neurotransmitter reuptake inhibitor, than did those taking SSRIs. But the clinical significance of the difference remained unclear. Venlafaxine demonstrated a 5.9% advantage in remission rates in direct clinical comparisons with SSRIs, Charles Nemeroff, M.D., Ph.D., of Emory University, and colleagues, reported in the Feb. 15 issue of Biological Psychiatry. In a small number of trials that included a placebo arm, venlafaxine achieved a 13% difference in remission rates compared with a 6% difference between SSRIs and placebo.
"One would expect to treat approximately 17 patients with venlafaxine to see one more success than if all had been treated with another SSRI," the authors said. "Although this difference was reliable and would be important if applied to populations of depressed patients, it is also true that it is modest and might not e noticed by clinicians in everyday practice."
"Nonetheless, a number needed to treat of 17 may be of public health relevance given the large number of patients treated for depression and the significant burden of illness associated with this disorder," they added.
The approved antidepressants are widely perceived as having similar efficacy, the authors said. However, few individual studies of newer antidepressants have had sufficient statistical power to demonstrate a difference in efficacy between effective therapies.
A meta-analytical approach offers the potential to reveal meaningful differences that individual randomized controlled trials could not, the authors continued. Previous meta-analyses have suggested that venlafaxine, which inhibits reuptake of serotonin and norepinephrine, has an efficacy advantage over SSRIs.
The current study, funded by Wyeth, continued the meta-analytical approach and involved two strategies for analyzing the data. One meta-analysis included all double-blind Wyeth-sponsored trials comparing venlafaxine and SSRIs. The authors said the limited analysis was undertaken to ensure access to individual patient data.
For the second analysis, the investigators used a funnel plot analysis to extend the primary dataset by including data from all studies in the public domain. The funnel plot analysis was based on 48 studies, including 14 additional studies, 11 of which were not funded by Wyeth. No evidence of statistically significant selection bias was observed in the updated analysis of 48 studies, suggesting to the authors that study sponsorship did not significantly influence outcomes.
The study included 34 randomized, double-blind studies of 4,191patients treated with venlafaxine or 3,621 given an SSRI. Nine studies with 932 patients also included a placebo control arm. The primary outcome was intent-to-treat remission rates at week eight, as defined by a Hamilton Rating Scale score of ≤7.
The overall difference between venlafaxine and the SSRIs as a class was statistically significant (P<0.001). When the SSRIs were considered separately, venlafaxine had a statistically significant advantage only versus fluoxetine (6.6%, 95% CI 0.030 to 0.095). Significantly more patients withdrew because of adverse events with venlafaxine than with SSRIs (11% versus 9%, P=0.0011).
Acknowledging limitations of the study, the authors said the generalizability of the findings to clinical practice is unknown as patients with more complex conditions were excluded from the trials. The trials involved short-term treatment, and the possibility of SSRI "catch up" with longer treatment could not be ruled out. They also acknowledged potential questions about the validity of combining all the SSRIs into a single group for the analysis.
Dr. Nemeroff had a lengthy list of financial disclosures that included relationships with Wyeth, which sponsored the study.
Primary source: Biological PsychiatrySource reference:Nemeroff CB, et al "Comprehensive analysis of remission (COMPARE) with venlafaxine versus SSRIs" Biol Psychiatry 2008; 63: 424-434.

Problem-Solving Treatment Helps Prevent Depression in Patients With Age-Related Macular Degeneration

August 8, 2007 — Problem-solving treatment (PST) may help prevent depression in patients with age-related macular degeneration (AMD), according to the results of a randomized controlled trial reported in the August issue of the Archives of General Psychiatry. This treatment prevented depressive disorders and loss of valued activities in the short term, but these benefits were not maintained over time, suggesting that booster treatments may be needed.
"Age-related macular degeneration is a prevalent disease of aging that may cause irreversible vision loss, disability, and depression," write Barry W. Rovner, MD, from Jefferson Medical College in Philadelphia, Pennsylvania, and colleagues. "The latter is rarely recognized or treated in ophthalmologic settings.... [AMD] provides an appealing model for depression prevention research because its severity is readily quantified, it affects men and women equally, and has no biological symptoms that overlap with depression and therefore avoids the problem of confounding behavioral outcomes with underlying disease symptoms."
At outpatient ophthalmology offices in Philadelphia, 206 patients aged 65 years or older were randomized to PST (6 home-based therapy sessions during an 8-week period; n = 105) or to usual care (n = 101). Participants were recently diagnosed with neovascular AMD in 1 eye and with preexisting AMD in the other eye.
The main endpoints were diagnoses of depressive disorders based on criteria from the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV); scores on the National Eye Institute Vision Function Questionnaire-17 (NEI VFQ-17), a subset of the 52-item scale; and rates of giving up valued activities. Short-term outcomes were evaluated at 2 months, and maintenance effects were evaluated at 6 months.
Compared with controls, the intervention group had a lower 2-month incidence rate of depressive disorders (11.6% vs 23.2%; odds ratio [OR], 0.39; 95% confidence interval [CI], 0.17 - 0.92; P = .03) and of giving up a valued activity (22 vs 37; OR, 0.48; 95% CI, 0.25 - 0.96; P = .04). Although most of these benefits had decreased at 6-month follow-up, patients who had received PST were less likely to have persistent depression (P = .04).
"Problem-solving treatment prevented depressive disorders and loss of valued activities in patients with age-related macular degeneration as a short-term treatment, but these benefits were not maintained over time," the authors write. "Booster or rescue treatments may be necessary to sustain problem-solving treatment's preventative effect. This study adds important new information to the emerging field of enhanced-care models to prevent or treat depression in older persons."
Limitations of the study include generalizability limited by the unique visual characteristics of the patient sample, the unclear effects of attrition, and the lack of a control treatment group receiving comparable attention without PST.
The National Institute of Mental Health, the National Eye Institute, and the Farber Institute for Neurosciences of Thomas Jefferson University supported this study. The authors have disclosed no relevant financial relationships.
In an accompanying editorial, Charles F. Reynolds III, MD, from the University of Pittsburgh School of Medicine in Pennsylvania, and colleagues note that teaching effective coping skills during brief, depression-specific, behaviorally oriented psychotherapy may be preferable to prescribing antidepressants.
"However, additional studies are needed to demonstrate durable protective effects," Dr. Reynolds and colleagues write. "Problem-solving therapy for primary care appears to be a good candidate for future testing, perhaps as a component of stepped-care interventions, in which patients first receive lower-cost, lower-intensity efforts, followed by stepped-up (more intensive) care based on need. Given the substantial barriers to good treatment of depression in old age, preventing depression may be a more sensible population-based approach."
The National Institute of Mental Health, the University of Pittsburgh Medical Center, and the John A. Hartford Foundation supported this editorial. The authors have disclosed no financial relationships.
Arch Gen Psychiatry. 2007;64:884-885, 886-892.

Liothyronine Plus Sertraline May Be Helpful for Major Depression

June 8, 2007 — In patients with major depressive disorder, liothyronine added to sertraline may be helpful in those most likely to benefit from combined therapy, according to the results of a randomized controlled trial published in the June issue of the Archives of General Psychiatry.
"It is possible to achieve a 20% increase in response and remission rates in major depression by the addition of liothyronine (T3) to treatment with the selective serotonin reuptake inhibitor (SSRI) sertraline," senior author Bernard Lerer, MD, a professor of psychiatry and director of the Biological Psychiatry Laboratory at Hadassah–Hebrew University Medical Center in Jerusalem, Israel, told Medscape. "This is a substantial clinical effect. Furthermore, liothyronine was not associated with increased adverse effects."
With SSRI treatment alone, fewer than 50% of patients achieve full remission, so there is a crucial need for antidepressant treatments that can achieve a higher remission rate than do currently available treatments. Previous studies suggest that the thyroid hormone triiodothyronine may potentiate antidepressant effects. The objective of the current study was therefore to determine the antidepressant efficacy and safety of liothyronine sodium (triiodothyronine [T3]) when given together with the SSRI sertraline hydrochloride to patients with major depressive disorder.
"Subject to regulations regarding off-label treatment, many clinicians already use liothyronine augmentation for treatment-resistant depressed patients, [and] our study suggests that liothyronine enhances response in patients who are not definitively resistant," Dr. Lerer said. "This is a relatively novel clinical concept — use of liothyronine as an enhancer to strengthen therapeutic outcome and not only as an augmenter in resistant patients. How to strengthen response and bring the maximum number of patients to remission is an important current concern in clinical psychopharmacology."
In this double-blind trial at outpatient referral centers, 124 adult outpatients meeting unmodified Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria for major depressive disorder without psychotic features were randomized to receive sertraline hydrochloride (50 mg/day for 1 week, 100 mg/day thereafter) plus liothyronine sodium (20 or 25 µg/day for 1 week, 40 or 50 µg/day thereafter) or sertraline plus placebo for 8 weeks.
The main end point was categorical response to treatment, defined as a 50% or greater decrease in scores on the 21-item Hamilton Rating Scale for Depression (HRSD) from baseline to study end point. Secondary outcomes were remission rate, defined as a final HRSD score of 6 or less, and visual analog scale improvement (50% of greater improvement) or remission (75% improvement).
In the intent-to-treat population, HRSD response rates were 70% in the sertraline-liothyronine group and 50% in the sertraline-placebo group (P = .02; odds ratio [OR], 2.93; 95% confidence interval [CI], 1.23 - 7.35). Remission rates were 58% with sertraline-liothyronine and 38% with sertraline-placebo (P = .02; OR, 2.69; 95% CI, 1.16 - 6.49).
"The main take-home point is that concurrent treatment with T3 in addition to an SSRI antidepressant is associated with higher response and remission rates compared to treatment with the antidepressant alone," Michael Gitlin, MD, a professor of psychiatry at Geffen School of Medicine of University of California, Los Angeles, told Medscape. Dr. Gitlin was not involved with the study but was asked to provide independent commentary. "If this finding is replicated, we might consider starting patients on an antidepressant plus T3 in some cases."
Compared with patients treated with sertraline-liothyronine who did not have remissions, those who did have remissions had lower baseline T3 values (t48 = 3.36; P < .002). In the sertraline-liothyronine group, remission was associated with decreased serum thyrotropin values (F1,73 = 4.00; P < .05).
"Besides the clinically relevant findings, we observed an important association between the endocrine effects of liothyronine and its therapeutic effects, which could help to understand mechanism of action," Dr. Lerer said. "The relatively low sertraline dose should be taken into consideration when considering clinical implications."
In the current study, liothyronine supplementation did not affect the frequency of adverse events, including those that might be expected to be more frequent with liothyronine, such as palpitations, sweating, and nervousness. However, Dr. Lerer warned that "the duration of treatment with liothyronine needs to be circumscribed because potential adverse effects of long-term effects are not known. Monitoring of thyroid function is important even with short-term treatment."
There were 2 serious events that led to study withdrawal. One patient receiving sertraline-placebo developed severe suicidal ideation, and 1 patient receiving sertraline-liothyronine required emergency thoracic surgery for a reason unrelated to the study.
"The doses of T3 used in this study are associated with very few side effects," Dr. Gitlin commented. "Theoretically, some patients could become mildly hyperthyroid with all its attendant effects, but this would be very unlikely given the doses used."
Strengths of this study noted by Dr. Gitlin are the double-blind design, the use of multiple treatment sites, and the relatively large number of subjects in the study compared with other studies in this field. The main limitation is that it is only 1 study, without clear indication of how many of the participants were treatment-naive and how many were treatment-resistant.
Other limitations noted in the article include lack of washout period for previous antidepressant treatment before starting the study medication; maximum dosage of sertraline being 100 mg/day; sites differing in response and remission rates across the placebo and liothyronine conditions; hormone assays being performed in different laboratories; and unknown generalizability to other patient groups or to SSRIs other than sertraline.
In terms of future research, Dr. Gitlin recommended additional studies to see if the findings can be replicated and large studies to examine the efficacy of T3 when given to treatment nonresponders.
"We are impressed with the potential of liothyronine to enhance antidepressant outcome," Dr. Lerer concluded. "However, not all patients need enhancement and not all patients are helped by liothyronine. We need to find ways to identify those patients who need liothyronine and are more likely to respond to it."
The Stanley Medical Research Institute in Chevy Chase, Maryland, supported this study. Dr. Lerer and the other authors have disclosed no relevant financial relationships. Dr. Gitlin has disclosed lecturing with Pfizer sponsorship and having no conflicts of interest regarding T3.
Arch Gen Psychiatry. 2007;64:679-688.

Augmentation Treatment Improves Recovery in Some Elderly Patients With Major Depression

Some elderly patients with major depression who had inadequate response to or relapse with initial treatment were more than likely to recover if they had a second drug (bupropion, nortriptyline, or lithium) added to their standard treatment, according to the results of a study reported in the May issue of the American Journal of Psychiatry.
"Few data are available concerning the utility of augmentation in late-life depression treatment," write Mary Amanda Dew, PhD, from the University of Pittsburgh School of Medicine in Pennsylvania, and colleagues. "The authors examined likelihood, speed, and predictors of recovery in older adults receiving augmentation pharmacotherapy after inadequate response to standardized treatment with paroxetine plus interpersonal psychotherapy."
The investigators monitored depression levels during open-label treatment in 195 adults aged 70 years or older and grouped patients based on whether they required augmentation with bupropion, nortriptyline, or lithium.
Of 105 patients requiring augmentation, 77 (73.3%) required it because of inadequate treatment response, and 28 (26.7%) patients because of response followed by relapse (N = 28). Of these 105 patients, 69 (65.7%) received augmentation and 36 (34%) did not, mostly because of withdrawal of consent or medical comorbidities.
Compared with patients never requiring augmentation, patients receiving augmentation had lower recovery rates. Recovery occurred in 50.0% of patients receiving augmentation because of inadequate response, in 66.7% of those receiving it after early relapse, and in 86.7% of patients who never required augmentation. Compared with other patients, patients receiving augmentation because of inadequate response recovered more slowly, with slightly more adverse effects. Greater medical burden and anxiety predicted slower recovery.
"Despite a lower likelihood of recovery in elderly people receiving augmentation, the recovery by over one half of such patients suggests the value of augmentation for those able to tolerate it," the authors write. "Need for augmentation presages slower recovery in patients showing initial inadequate response; those requiring it after early relapse recovered more quickly. Strategies to further improve the likelihood and speed of recovery after initial treatment failure are needed."
Study limitations include primarily European American sample, lack of placebo control, administration of augmentation by nonblinded clinicians and patients, and limited group sizes within the major study subgroups.
"Our findings suggest the promise of augmentation strategies in the treatment of late-life depression, but they indicate that the application of these strategies will ultimately depend on older adults' medical status and personal preferences for treatment," the authors conclude. "Within these constraints, we recommend that controlled studies of the efficacy of augmentation strategies be undertaken. Such studies are needed both in the context of failure of initial SSRI treatment and in first-line attempts to promote improved likelihood and speed of recovery."
The National Institute of Mental Health supported this study. Some of the authors have disclosed various financial relationships with Astellas Pharma, Pfizer, Johnson & Johnson, Forest Laboratories, Eli Lilly, Janssen Pharmaceuticals, AstraZeneca, Lundbeck, GlaxoSmithKline, and/or Bristol-Myers Squibb.
Am J Psychiatry. 2007;164:1-8.