UW 3rd Annual Update – Treatment Resistant Depression

There were couple presentations relevant to depression that were given at the UW interview this year.  The first was from Karen Dineen Wagner, MD, PhD from the University of Texas Medical Branch in Galveston, Texas.  Her word was a mix of the ~-fashioned and the new.  The fertile is the state of pharmacology of depressed children seems to be favored with changed very little over the exceeding 20 years.  This seem largely appropriate to the fact that there bear been few successful antidepressant trials in children.  This has led to the set forth where there are only two FDA approved medications fluoxetine and escitalopram based up~ a total of 4 clinical trials.  She  showed one additional 14 clinical trials of indicative antidepressants including 3 that were definite for citalopram and sertraline but each additional negative study for the FDA approved medication escitalopram.  The dead-stand in many of these trials is a tyrannical placebo response rate in the trials (40% greater than in ripened clinical trials).  She recommended one informed consent approach explaining to the parents somewhat time an off label approach was being used and the rationale for using somewhat medication based approach.  She in addition recommended starting with the FDA approved medications because pediatric depression.

Her suggested approach to dolefulness in children and adolescents is to differ out with an FDA approved SSRI plus cognitive behavior therapy (CBT).  This is the chiefly evidence based approach with the evidence rapidly disappearing at subsequent levels in which place the usual augmentation and substitution steps that are typically used in adults were suggested.  The Treatment by reason of Adolescents with Depression (TADS) study was presented with the recovery rates for fluoxetine, fluoxetine + CBT, and CBT alone at 12, 18, and 36 weeks were presented.  The fluoxetine + CBT weapon had superior results at 12 and 18 weeks end at 36 weeks the recovery rates were similar at 86% versus 81%.  Those are religious results for any antidepressant trial and the placebo replication rate in this study was additional similar to the adult placebo answer rate.  The results of this study were presented to the degree that a rationale for using antidepressants in adolescents through severe depression and/or suicidal ideation from the time of the response rate for fluoxetine + CBT were faster than fluoxetine or CBT alone at 12 and 18 weeks and essentially the same at 18 and 36 weeks.

The effect of strategies for addressing SSRI resistant dolefulness were presented in the form of a preceding trial where 334 adolescents with SSRI management failures were randomized to a manifold SSRI or venlafaxine or SSRI + CBT or venlafaxine + CBT.  The testing done by Brent, et al showed that in that place was no difference in response rates switching to not the same SSRI or venlafaxine but switching antidepressants and adding CBT produced more exalted results.  Sides effects were greater notwithstanding the venlafaxine arm with a small increase in diastolic blood pressure and centre of circulation rate and a four fold enlarge in skin rashes – a complication that I own rarely seen in adults.  The overall impression was that CBT was the ~ly effective intervention for adolescent depression but I am sure that most psychiatrists in the host were left wondering: “If I be possible to’t find CBT therapists for my of mature age patients with depression – what are the probability I can find them for my adolescent patients?  To me that has for aye been the critical shortage in psychiatry – not the designate by ~ of people who can prescribe medications.

Paul Holtzheimer, MD supposing the adult perspective in the vesicatory Management of Treatment Resistant Depression in Adults.  He made the epidemiological respect that treatment resistant depression (TRD) is offering in 10-33% of patients with major depressive disorder and in the U.S. that is relative to 1-3% of the population.  He had a fairly full agenda covering pharmacotherapy and augmentation strategies, electroconvulsive therapy, greater degree of recent non-invasive electromagnetic therapies and not sharp brain stimulation.  There was ~ness new on the medication front.  After reviewing the basic medication groups, he suggested that the newest antidepressants offered ~t one advantage over earlier medication.  He suggested that monoamine oxidase inhibitors (MAOIs) were inner reality underutilized as a treatment for dejection unresponsive to standard agents.  In the moderated ventilation Ned Kalin, MD – the head of the province of psychiatry at the University of Wisconsin agreed.  The speaker said that he typically used phenelzine and tranylcypromine.  I personally require not prescribed either of these agents in more time.  I recall using them in situations in what place the person has treatment resistant gloominess and did not have any responders.  In those situations, response rates tend to be low anyway.  The other enigma is that you have to imagine that your chronically depressed patient is going to be motivated and cognitively intact enough to take hold to the necessary diet, report the kind of could be significant side effects and not try to slay themselves with the medication.  During the debate there was a report of common patient who decided to eat great tyramine content food (prohibited on this diet owing to a the risk of a hypertensive reverse action) – have a stroke and die.  The unrepining in this case did have a sudden effort but did not die.  I personally comprehend of situations where strokes have occurred, in such a manner this strategy is not without exposure to harm.

The augmentation strategies discussed were up~ out of STAR*D with the anomaly of using atypical antipsychotics with antidepressants.  Dr. Holtzheimer said that this was probably the in the greatest degree common augmentation strategy and the risks were discussed.  He and Dr. Kalin were advocates of augmentation with lithium and triiodothyronine (T3).  There were three slides without ceasing STAR*D showing cumulative remission and moderation rates across all levels of care.  Those rates were 33% by initial monotherapy and 66% after 4 treatments and considered in the state of expected less remission rates at cropped land level of treatment change.  Dr. Holtzheimer made the stop that the current rates of rest with medication and psychotherapy have in fact not changed since the 1950s and that makes electroconvulsive therapy (ECT) the most effective antidepressant treatment with a 50-75% stoppage rates and a >50% backslide rate in the first 6 months.  He touched without interrupti~ novel pharmacological agents categorized by neurotransmitter, neuroendocrine, or immunological systems.  He did not pronounce much about ketamine (there is every intranasal preparation in clinical trials in accordance with duty now) but did mention that in that place is a IL-6 (cytokine) antibody temptation going on right now.

He moved adhering to talk about more invasive therapies.  He presented a lively that was a drawing by Papez.  To anyone skilled in neuroanatomy around the time I was in of the healing art school, many anatomy professors would at hand a saggital section of the brain and commit to the limbic structures as the Papez region.  At first I thought the etc. had a surprising amount of item for a 1937 publication but therefore I went to the original piece online (AMA web site) and institute that the original drawing was not used.  The 1937 drawing had the surface anatomy correct if it were not that no tracts.  Papez mentions the amygdala three epochs in the last few paragraphs of his clause.  He used this slide at the same time that a prelude to an article ~ dint of. Mayberg (3) providing a rational in favor of deep brain stimulation as treatment on this account that depression.  I plan to arrive up with a separate post in this technology based put ~ several sources but right now in that place are a number of centers looking a sea brain stimulation for depression and absorption.  Dr. Holtzheimer briefly commented up~ transmagnetic stimulation (TMS).  There are manifestly 4 FDA approved devices, use is expanding and assurance reimbursement is expanding.  He declared ti was 50% effective for management resistant depression.  I am in a great degree skeptical of that number based without ceasing the people I see, but I moreover realize that I am seeing a in a great degree treatment resistant with multiple comorbidities.  Seizure put in peril was listed as the most weighty side effect.

Vagus nerve stimulation (VNS) has been on every side for about a decade.  I get seen a few of these patients and never referred anyone for placement of this shift.  There is limited third share reimbursement and in my opinion waning religious frenzy for this technology.  The in conclusion time I interviewed a person with VNS, their speech quality changed every time the stimulator was active.  That is a momentous side effect and I don’t comprehend if that has been addressed by current technology.   Transcranial direct current stimulation (tDCS), transcutaneous vagus invigorate stimulation, and cranial electrical stimulation were every part of listed as having limited data.

Deep brain stimulation (DBS) was clearly the ~ duct focus of Dr. Holtzheimer’s introduction.  The first article suggesting that it may be effective for obsessive compulsive disorder (OCD) was in the Lancet in 1999.  Based forward that research DBS of the going before. internal capsule is an FDA approved indicating. see preceding verb for DBS.  An open label study suggested that it may in addition be effective for TRD and there were no adverse effects or neuropsychological movables.  Three additional pilot studies of DBS to the core accumbens suggested that it may have existence useful for TRD and features of TRD like fear and anhedonia.  Since then in that place have been two randomized controlled trials of DBS to the abdominal striatum subcallosal cingulate gyrus (SCC).  The first study (ventral striatum) was negative and the encourage (SCC) was stopped.

The overall termination had to be that TRD was ever a common and disabling condition.  The mainstays of treatment at this point are still the medications and ECT that we receive had throughout my career.  My experience is that I can help greatest in number people get well, but there are important obstacles even to standard care.  Every lecturer to this place emphasized the utility of cognitive behavioral therapy.  Like greatest in number psychiatrists, I can do cognitive behavioral therapy ~-end by myself I can’t gratify the demand.  The people accountable for mental health policy and security against loss standards certainly do not want to public ~s the recommended research courses of CBT towards chronic depression.  There is not at all distinction for TRD versus non-TRD lowness and no differential resource allocation.  That leaves most patients with TRD and non-TRD hollow looking for “prescribers” who can consider them for 10-30 minute appointments to generate advice on how to recover and try numerous prescriptions.  None of the beneficial care matches what top researchers counsel in these CME seminars, in articles, or in books.

We could terminate a lot better trying to live up to that ensign while additional diagnostic and treatment strategies are developed.            

George Dawson, MD, DFAPA


1:  David Brent Adolescent dolefulness references  

2:  Papez JW. A proposed mechanism of emotion. 1937. J Neuropsychiatry ClinNeurosci. 1995          Winter;7(1):103-12. PubMed PMID: 7711480.

3: Mayberg HS. Targeted electrode-based modulation of neural circuits toward depression. J Clin Invest. 2009 Apr;119(4):717-25. doi: 10.1172/JCI38454. Review. PubMed PMID: 19339763

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