Top psychiatric findings from the 2022 Carlat Report
Publication Date: 1/9/2023
Duration: 26 mins, 50 seconds
CHRIS AIKEN: From January to December, these are the updates that changed our practice in 2022.
Welcome to the Carlat Psychiatry Podcast, keeping psychiatry honest since 2003. I’m Chris Aiken, the editor in chief of the Carlat Report. And I’m Kellie Newsome, a psychiatric NP and a dedicated reader of every issue.
Kellie we have a lot to cover in this episode so let’s get right into it.
KELLIE NEWSOME: We started 2022 with a review of SAMe. This antioxidant methyl donor is involved in the production of the three major monoamines: serotonin, dopamine, and norepinephrine. In that sense, it functions a bit like a traditional antidepressant, and one of the big takeaways from this article is that it works about as well as an antidepressant. That is based on head-to-head studies, as well as metaanalyses – where SAMe comes up with a respectable medium effect size.
CHRIS AIKEN: SAMe is better tolerated than most antidepressants, particularly when it comes to sexual side effects. In one study, SAMe successfully treated SSRI-induced sexual dysfunction. SAMe can be safely added to an antidepressant, and there is good reason to do so. In a controlled trial, it augmented antidepressants in people who had not responded to a single trial. That’s a single trial, not two trials, so we can’t go so far to say that SAMe works in treatment resistant depression. Another reason to consider SAMe is that it has benefits in some medical conditions that often go along with depression, like HIV, liver disease, Parkinson’s disease, and arthritic pain.
We found one reason to avoid SAMe: Bipolar disorder. It has been known to trigger mania, which we might expect from its monoaminergic mechanism. And I have seen manic symptoms on it in practice.
SAMe sits with a few other natural therapies that work as well as medication. I’d add light therapy, l-methylfolate, and St John’s Wort to that list for depression; and for anxiety I’d add Silexan – a lavender extract we covered in 2021 that has a large effect size in generalized anxiety disorder. I’m basing these rankings on my own experience with hundreds of patients who took them, as well as the effect sizes in the studies.
We tend to lump all natural treatments together, but some are more natural than others. Herbs like St John’s Wort and Silexan are natural to the ground, but not to the body, whereas nutrients like SAMe and omega-3 fatty acids are already in the body. SAMe is the primary methyl donor in the body, and when we use it for treatment we are having patients take more of what they already have. In my own thinking, I lump herbal treatments with medications, and keep nutrients like SAMe and methylfolate separate. After all, many medications including valproic acid and bupropion (Wellbutrin) were derived from plants that had been used in herbal medicine for centuries.
KELLIE NEWSOME: SAMe costs about $30-40 a month. Check out Garrett Rossi’s article in our January 2022 issue for details on how to use it.
KELLIE NEWSOME: In February we took on two practice trends that have fallen behind the data: Clozapine and gabapentin.
CHRIS AIKEN: Dr. Brian Miller reminded us to use clozapine in treatment resistant schizophrenia. And we need to be reminded – because 30% of people with schizophrenia have the treatment resistant type, but only 5% in the US get clozapine. There is no excuse for this – yes, psychiatrists tell me there patients won’t be able to get the labs done, and I can almost sympathize, but no – when they have a meaningful recovery on clozapine they will be able to get the labs done and even go back to school and work. In other countries, 25% of people with schizophrenia get clozapine, so there is no reason we can’t pick up the pace in the US.
Treatment resistance means two failed antipsychotic trials. It can be two atypicals, as long as they took a full course and did not have a meaningful response. What does that look like? It means the patient is still not able to function independently – they keep going back to the hospital or their family has trouble managing them because of active psychotic symptoms. Unfortunately, full recovery is rare in schizophrenia, so even if they respond to an antipsychotic they may continue to have impairments – often the psychotic symptoms recede to the background. They no longer listen to the voices, but they still have negative symptoms. Dr. Miller saw hope there – he has seen many patients who are able to go back to school or return to work after starting clozapine. Dr. Miller also shared his favorite antipsychotics to try before clozapine, and a few strategies who uses when patients don’t respond to clozapine.
KELLIE NEWSOME: The other area where practice lags science is with the gabapentinoids – gabapentin (Neurontin), pregabalin (Lyrica), and tiagabine (Gabitril). Psychiatry developed a liking for gabapentin 20 years ago and it has not given up. It’s rare to see psych patients who have not tried it, and equally rare to see psych patients who HAVE tried its cousin, pregabalin.
CHRIS AIKEN: The paradox here is that gabapentin has only a few small trials in psychiatric disorders – mainly social anxiety, and cannabis and alcohol use disorders – while pregabalin has much better evidence. But admittedly there is not as much at stake here as there is with the clozapine matter, so let’s quote from Dr. Rajesh Tampi’s article in our February 2022 issue.
KELLIE NEWSOME: “Pregabalin has much better evidence in anxiety disorders, with eight randomized controlled trials at a dose range of 150–600 mg/day involving over 2000 patients with generalized and social anxiety disorders, including several with long-term follow-up (Generoso MB et al, Int Clin Psychopharmacol 2017;32(1):49–55). Pregabalin sees more use for anxiety in Europe, where it has regulatory approval in generalized anxiety disorder, while US psychiatrists lean toward gabapentin. The evidence is clearly in pregabalin’s favor, but gabapentin does have a tolerability advantage, with lower rates of weight gain and ataxia”
From Rajesh Tampi, who chairs the Department of Psychiatry at the Cleveland Clinic in Akron. Dr. Aiken, what about that third gabapentinoid – tiagabine (Pregabalin). It barely gets a mention in this article.
CHRIS AIKEN: I almost never see that prescribed in psychiatry, and there’s a reason why. Tiagabine actually got off to a running start 20 years ago. There were small pilot studies in sleep and anxiety, and large industry sponsored dinner programs and promotional booths at the APA – this is when off label promotion was less regulated. But then a paradoxical warning brought that to an end. Although tiagabine is an anticonvulsant, there were reports of the drug inducing seizures in people who did not have epilepsy. No one wanted to trigger a seizure with an off label drug, so they stopped promoting it in psychiatry. If you do use it, here’s a tip – you may be able to avoid that seizure risk with a slow titration.
KELLIE NEWSOME: In March Dr. Aiken reviewed omega-3’s. Here are 3 takeaways:
1. They work in depression – both bipolar and unipolar – with a decent effect size in the small to medium range
2. However, they only work if you get the right ratio and dose. The product needs to have at least twice as much EPA omega 3 as DHA.
3. All supplements have problems with quality control, so check our March issue where we’ve listed omega-3 brands that were tested by independent labs
Dr. Aiken it’s been a year since you wrote this do you have any further updates?
CHRIS AIKEN: Yes. I mentioned in the article that omega is more likely to work in patients with inflammation – such as obesity or an elevated CRP. In August Dr. Mark Hyman Rappaport and colleagues at Mass General ran a controlled trial testing different doses of omega 3 in this population – overweight patients with inflammation. They found that a high dose worked best – 4,000 mg/day – which is above the 1,000-3,000 mg dose we arrived at for average patients.
KELLIE NEWSOME: In April, Dr. Rehan Aziz reviewed antidepressant dosing. Dr. Aziz is an Associate Professor of Psychiatry at Rutger’s Robert Wood Johnson Medical School. Here’s the take “For most antidepressants, raising the dose beyond the low-to-medium range does not bring more benefits in depression. The tricyclics, MAOIs, and venlafaxine are exceptions.” Check out Dr. Aziz’s table in our April issue where he listed those ideal dosing ranges, and our interview with Dr. Tam Kelly on how to use thyroid augmentation in treatment resistant bipolar depression.
In May Dr. Steve Wyatt brought us an update on Varenicline (Chantix). We almost didn’t run this piece because this smoking cessation agent was pulled from the market right after Dr. Wyatt finished it. But Varenicline is back on the market and in generic form. It was actually the brand that got pulled, in late 2021, and it was taken off voluntarily because of contamination with nitrosamines, a carcinogen that has tainted the production of numerous medications in recent years, including ranitidine, nizatidine, and metformin. Here are 2 takeaways from Dr. Wyatt’s piece:
1. Varenicline is about twice as effective as other smoking cessation agents, including bupriopion. It even works better in depressed patients than bupropion.
2. Varenicline does not worsen mental illness – yes it did have a black box warning about suicidality 10 years ago but that has since been downgraded after studies in thousands of patients – most notably the Eagles trial – did not find any problems.
CHRIS AIKEN: Also in the May issue was a practical guide to tricyclic antidepressants by Dr. Edmund Higgins, associate professor, Psychiatry and Behavioral Sciences, Medical University of South Carolina. Coauthor of the textbook The Neuroscience of Clinical Psychiatry. Dr. Higgins listed 6 reasons to use a tricyclic, including my personal favorite - Prevention of depression after ECT, where the combination of nortriptyline and lithium kept depression away for the long-term in non-bipolar patients. And that’s a place to avoid tricyclics, bipolar, as they have higher risks than most antidepressants of inducing mania. Check out his article for tips on managing their side effects and how to choose the best tricyclic – for most patients your go-to should be nortriptyline, but some side effects or comorbidities might lead you to others.
CHRIS AIKEN: For our June July double issue, we covered another area where practice does not line up with the data. Psychotic Depression. Conrad Swartz wrote a textbook on the subject, but he’s one of those academicians who also sees a lot of patients so his interview is full of useful pearls. Here’s one. Chances are you are missing a lot of psychotic symptoms. A study of hospital units at four academic medical centers found that one in three cases of psychotic depression went undiagnosed. And if you do diagnose it, you may not be giving the best treatment. Yes, there are good reasons to use antipsychotics, but Dr. Swartz outlined a convincing case for why they are second line to ECT. And the evidence that antipsychotics actually work – or are necessary – in psychotic depression is a lot thinner than their name suggests. If you do use an antipsychotic, aim for the higher dose range like you would for schizophrenia, not the lower doses we see in antidepressant augmentation.
KELLIE NEWSOME: Also in June we learned about two meds that we often turn away from because of their risks, but sometimes need to use because their benefits are unmatched: benzodiazepines and quetiapine Seroquel. Dr. Paul Riordan from Duke University reminded us that quetiapine it is the only antipsychotic outside of cariprazine with evidence in bipolar mania and depression; it is the only antipsychotic with good evidence for long-term prevention in bipolar; and the only one with good evidence to improve anxiety, as well as some evidence for sleep – not just sedation but also sleep quality.
Dr. Carl Salzman, a professor at Harvard and past chairman of the APA Benzodiazepine Task Force, warned us not to give in to the anti-benzo hysteria and gave a rational plan for when to use them and when to avoid them.
CHRIS AIKEN: In August we interviewed Richard Brown on natural therapies for ADHD. Dr. Brown is a Professor of Psychiatry at Columbia University who began his career as a psychopharmacology researcher and then turned those evidence based tools to investigate natural compounds. Dr. Brown also has a busy practice, so he was able to tell us not just what has evidence to work in ADHD but what he’s actually seen work. Mainly, he uses naturals to treat comorbid problems in ADHD that stimulants don’t address, like dyslexia with racetram nootropics and working memory with American ginseng.
KELLIE NEWSOME: Next, Dr. Garrett Rossi covered all the things you need to think about when antidepressants don’t work – besides bipolar disorder. High on his list were obesity, vascular health, inflammation (which he measures with a high sensitivity C reactive protein), trauma history, and social isolation.
CHRIS AIKEN: In September James Phelps dug up the evidence on low dose lithium to prevent dementia. The bottom line: It’s not ready for a full FDA style roll out, but it is worth trying in select patients who are high risk for dementia and want to try something that has a chance of preventing it.
KELLIE NEWSOME: For our October-November double issue Dr. Aiken teamed up with Dr. Uma Naidoo to create a dietary plan for ADHD. This article was inspired by a new randomized controlled trial that used the DASH diet to successfully improve ADHD symptoms in children. The study used a meaningful placebo – the control group was put on a sham diet.
CHRIS AIKEN: Besides the DASH study, we also have decades of research suggesting that food colorings and other artificial ingredients worsen ADHD as well as general cognition. Dr. Naidooand I blended all this research together to create a simple dietary plan that your patients will appreciate. Dr. Naidoo is a psychiatrist and Director of Nutritional and Metabolic Psychiatry at Harvard’s Massachusetts General Hospital (MGH).
KELLIE NEWSOME: Dr. Aiken also wrote a controversial piece on the Benzodiazepine-Stimulant Combo.
A lot of patients take these controlled substances in combination, and pharmacists are starting to scrutinize this combo – and sometimes even refuse to fill it – now that the DEA is cracking down on overprescription of these controls that took place during COVID. I decided to look into this with an open mind – asking “What could go wrong?” Sure they are uppers and downers, but do they really cancel each other out? I mean if you take them for the right reason the stimulant should calm down the hyper symptoms of ADHD, and the benzo should help someone with panic disorder get out of the house and get moving in their lives.
CHRIS AIKEN: What I found shocked me. First, if estimates from a large Rhode Island database are generalizable, around 1 in 115 Americans were prescribed both a stimulant and a benzo in the last year. Second, there is zero clinical research on this combination. Zero. So I relied on basic science, animal studies, and studies in people with recreational use of the two. Bottom line: It’s not a good idea to prescribe these two together, but if you do oxazepam and methylphenidate are the safest, alprazolam and amphetamines like Adderall and Vyvanse are the worst. And unfortunately – you guessed it – the alprazolam and amphetamines are the most common version of this unwise combo.
Here’s another pearl – you may not be aware of how much you are prescribing them together until you start looking, and if you are the article outlines a few cases where continuing the two is the lesser of evils.
KELLIE NEWSOME: In December we interviewed Dr. Allen Frances, who once chaired the DSM committee and now is one if the guide’s most vocal critics. Dr. Frances shared ideas for how to incorporate psychotherapy in the brief medication visit, and he took a swing at a cherished notion in psychotherapy research. You often hear that therapists have better outcomes when they follow a manual, because they are less likely to drift into unproductive realms. Dr. Frances found a major hole in that research, and explains why manualized psychotherapy may be counter-therapeutic for patients with complex conditions. Audio learners can hear more of Allen Frances in his podcast Talking Therapy.
CHRIS AIKEN: The December issue also covered a disorder that responds much better to psychotherapy than medication – trichotillomania. Dr. Michael Posternak explains how to do the behavior therapy for hair pulling, and uncovers at least one somatic therapy that might work – the antioxidant N-Acetylcysteine. Dr. Posternak is an academic psychiatrist who now works in private practice, and we always learn something new in his work.
It’s hard to find psychiatrists who are skilled in research and practice, and who don’t have a lot of industry conflicts. Our double issue for Oct-Nov featured two of them who shared practical tips on mood disorders - Ronald Pies on bipolar depression and Charles DeBattista on treatment-resistant depression. Dr. DeBattista worked on Stanford’s SAINT protocol for TMS which earned FDA approval last Fall based on a 2022 study from his group.
KELLIE NEWSOME: Let’s end with that study Dr. Aiken. I believe you crowned it the top research finding for 2022 in your DailyPsych feed on LinkedIn.
CHRIS AIKEN: This was a randomized controlled trial that lead to FDA Approval last September for SAINT TMS. The SAINT protocol differs from regular TMS in 3 important ways
1. It uses high intensity theta-burst stimulation, which allows the delivery of a treatment dose in 3 minutes rather than 20-45 minutes with other devices.
2. It uses MRI coils to guide the TMS magnet. This is much more precise than using anatomical guides, which may miss the mark 30% of the time.
3. Here’s the biggest difference. Instead of giving TMS once a day for 6 weeks, SAINT gives it once an hour for one week.
The bottom line: 79% of these patients achieved remission at some point within the first month after undergoing SAINT, compared to 13% in the sham/placebo group. That’s an unusually large remission rate, so much so that it made Dr. DeBattista suspicious, and he saw it with his own eyes. Normally we’d expect remission rates of 20-30% in this group.
So is it too good to be true? We’ll see in 2023 when the SAINT machines roll out.
KELLIE NEWSOME: Do you know anyone you’d like to see us interview? We’re looking for those triple-threats – skilled in patient care, well versed in research, and short on industry funding. Let us know at email@example.com or DM Dr. Aiken on LinkedIn. Earn CME for this episode through the link in the show notes, or subscribe to the print journal online and get $30 off with the promo code PODCAST. Your support helps us keep bringing the news on all things psychiatric without industry support.