Treatment-Resistant Depression Carlat Reports

Clinical Update

What Gets in the Way of Antidepressants?

From The Carlat Psychiatry Report, ADHD

When patients don’t respond to an antidepressant, it’s a good idea to step back and look for anything that might be getting in the way. Major stress, substance use, medication nonadherence, anxiety, and medical and psychiatric comorbidities are high on that list, but recent research has added more possibilities that we’ll review in this article.

Research Update

Can TMS Turn on the Switch?

From The Carlat Psychiatry Report, Psychotic Depression

Topics: Depression | rTMS | TMS | Transcranial Magnetic Stimulation | Treatment-Resistant Depression

REVIEW OF: Miuli A et al, World J Psychiatry 2021;11(8):477–490 STUDY TYPE: Literature review and meta-analysis Some treatments for depression, particularly antidepressants, present risk of manic reactions, but whether this risk exists with transcranial magnetic stimulation (TMS) is less clear. A group in Italy searched the world’s literatu

Clinical Update

Tricyclic Antidepressants: When and How to Use Them

From The Carlat Psychiatry Report, Race and Mental Health

Topics: Antidepressants | Dosing | Side Effects | Treatment-Resistant Depression | Weight gain

Tricyclics have been used in psychiatry since the 1950s, when imipramine was introduced as the first mass-marketed antidepressant. Fluoxetine and the other SSRIs largely supplanted the tricyclics in the 1990s, but these medications still have their uses. There are two kinds of tricyclics: Tertiary amines—the “originals” Secondary amines—t

Expert Q&A

Getting Uncomfortable with Esketamine

From The Carlat Psychiatry Report, Esketamine

Esketamine (Spravato) was approved for treatment-resistant depression in 2019. In this interview, Dr. Williams (who has no relationship with Janssen Pharmaceuticals, Inc) addresses some lingering doubts that have been raised about the medicine. TCPR: Where does esketamine fit in the list of interventional therapies for depression, like repetitive tra

Research Update

TMS: Deeper is not Better

From The Carlat Psychiatry Report, Esketamine

REVIEW OF: Filipcic I et al, J Psychiatr Res 2019;114:113–119 TYPE OF STUDY: Randomized single-blind controlled trial Seven transcranial magnetic stimulation (TMS) devices are FDA approved for depression, but only one—the Brainsway—is distinctly different from the others. Brainsway uses a patented H1 coil that penetrates deeper into the cortex t

Research Update

Structural Brain Changes After ECT for Depression

From The Carlat Psychiatry Report, Thyroid and Mental Illness

Topics: ECT | Neuroscience in Psychiatry | Psychotic Depression | Treatment-Resistant Depression

REVIEW OF: Gryglewski G et al, Brain Stimul 2021;14(4):927–937 STUDY TYPE: Meta-analysis Electroconvulsive therapy (ECT) has high antidepressant potency, boasting an impressive response rate of up to 80%. However, despite decades of research, we still have little understanding of its mechanism of action. Although several structural brain changes hav

Research Update

Psilocybin vs Escitalopram for Depression

From The Carlat Psychiatry Report, Overdiagnosis

REVIEW OF: Carhart-Harris R et al, New Engl J Med 2021;384(15):1402–1411 STUDY TYPE: Randomized controlled trial Psilocybin is, among other things, a serotonin 2A agonist responsible for the psychedelic properties of magic mushrooms. Back in 1960, Sandoz (now Novartis) began marketing psilocybin to enhance the effects of psychotherapy, but produ

Research Update

Pilot Study of Ketamine vs ECT for Major Depression

From The Carlat Psychiatry Report, Overdiagnosis

Topics: ECT | Esketamine | Ketamine | Suicide | Treatment-Resistant Depression

REVIEW OF: Kheirabadi D et al, J Clin Psychopharm 2020;40(6):588–593 STUDY TYPE: Randomized controlled trial Electroconvulsive therapy (ECT) has long been the gold standard for severe or treatment-refractory depression (TRD). However, it has two major drawbacks: it involves anesthesia and it may be associated with memory impairment. Ketamine has

Clinical Update

ECT Worked: Now What?

From The Carlat Psychiatry Report, Therapy

Juan is a 72-year-old man with severe depression who has not responded to numerous antidepressant trials. He is reluctant to undergo a course of electroconvulsive therapy (ECT), but agrees to do so if one last medication trial doesn’t work. After failing to respond to escitalopram augmented with aripiprazole, Juan receives a course of ECT and has a te

Expert Q&A

Psychotherapy and Medication in Recurrent Depression

From The Carlat Psychiatry Report, Depression

TCPR: When depression is recurrent, we usually continue the antidepressant indefinitely. Has that practice come under challenge? Dr. Fava: Yes. Antidepressant drugs are certainly important during the depressive episode, but what we are starting to question is whether they are as effective in preventing relapse. A meta-analysis from 12 years ago found t

Expert Q&A

Genetic Testing: What You Need to Know in 2021

From The Carlat Psychiatry Report, Depression

TCPR: Is there a role for genetic testing in clinical practice? Dr. Nurnberger: I think the evidence is growing that there’s a place for this in clinical practice. The meta-analyses of pharmacogenetic tests are actually looking pretty favorable recently, at least for some genes, particularly CYP2D6 and 2C19 (Bousman CA et al, Pharmacogenomics 2019;20

Expert Q&A

When Further Medication Trials Seem Futile

From The Carlat Psychiatry Report, Borderline Personality Disorder

TCPR: When it comes to medication trials, how do you know when enough is enough?Dr. Goldberg: I don’t think I would ever say “enough is enough,” but there is a point at which the probability of medicines having a big effect becomes very, very low. In depression, that point is pretty black-and-white in my mind: 5 trials. In a study from Massachuset

Expert Q&A

Inflammatory Biomarkers in Depression

From The Carlat Psychiatry Report, Inflammation and Depression

TCPR: What is inflammation? Dr. Miller: Inflammation is the body’s natural response to infection or wounding. It’s important for survival, but if it goes on too long it damages the body in various ways. It contributes to heart disease, cancer, metabolic disorders, and neurodegenerative disorders. Ultimately, it can change set points in the brain th

Highlights

Highlights From This Issue

From The Carlat Psychiatry Report, Inflammation and Depression

Inflammation contributes to treatment resistance in depression and can be measured with a blood test, C-reactive protein (CRP). An elevated CRP predicts a favorable response to certain antidepressants, as well as specific lifestyle interventions. Nuedexta’s expanded use in dementia is based on questionable efficacy, but it is safer than many

Research Update

Anti-Inflammatories as Antidepressants?

From The Carlat Psychiatry Report, Mental Health Apps

Topics: Antidepressants | Depression | Inflammation | Novel Medications | Treatment-Resistant Depression

Review of: Köhler-Forsberg O et al, Acta Psych Scand 2019;139(5):404–419 Study Type: Meta-analysis of randomized controlled trials Several lines of evidence suggest that chronic inflammation contributes to depression. For example, markers of inflammation tend to be elevated in depressed patients, and inflammatory syndromes elicit depressive sym

Article

Mirtazapine Augmentation: Running Low on Rocket Fuel

From The Carlat Psychiatry Report, How to Talk about Medication

Adding mirtazapine (Remeron) to a serotonergic antidepressant is a popular augmentation strategy. When added to venlafaxine, the combo was thought to possess a particularly potent synergy that Stephen Stahl called “California Rocket Fuel.” However, the strategy has failed in a handful of new studies, some of them much larger than the original data.

Article

l-Methylfolate for Depression: Costly Mistake or Good Thinking?

From The Carlat Psychiatry Report, Side Effects Part II

Folate (Vitamin B9) has a long track record as a low-cost, low-risk augmentation strategy in depression. It’s also available in a more expensive form, l-methylfolate (Deplin), that promises better results but at a premium price. So, is the cost worth it? Folate pathwaysFolate (the natural form of folic acid) is a B vitamin that’s important in psych

Article

Esketamine Gets FDA Approval

From The Carlat Psychiatry Report, Side Effects Part I

Topics: Depression | Depressive Disorder | Esketamine | Pharmacology | Treatment-Resistant Depression

On March 5, 2019, the FDA approved esketamine (Spravato) nasal spray as add-on therapy to traditional antidepressant medications for treatment-resistant depression (TRD). In this article, I will describe the events that led to esketamine’s development, review the data submitted to the FDA, and discuss what the future might hold for esketamine. Backgr

Article Links

Risk Evaluation and Mitigation Strategy (REMS) Programs

From The Carlat Psychiatry Report, Side Effects Part I

Topics: Depression | Depressive Disorder | Esketamine | Pharmacology | Treatment-Resistant Depression

Certain psychiatric treatments require both the healthcare provider and patient to enroll in a Risk Evaluation and Mitigation Strategy (REMS) program before they are administered. Below are links to enroll: Brexanolone (Zulresso) http://www.zulressorems.com/ Buprenorphine-based therapies (Suboxone, Subutex) https://www.samhsa.gov/medication-assi

Research Update

Lithium in Geriatric Depression

From The Carlat Psychiatry Report, Side Effects Part I

REVIEW OF: Buspavanich P et al, J Affect Disord 2019;251:136–140 TYPE OF STUDY: Prospective, non-randomized controlled trial Augmentation with lithium has long been established as an effective strategy for refractory depression, but how does it fare in geriatric patients? There is a dearth of evidence on lithium in the geriatric population, which