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3707_pharmacologic_treatment_of_hair-pulling_and_skin-picking.pptx
- 1. Pharmacologic Treatment of Hair-Pulling and Skin-Picking Disorders: SSRIs, N-Acetylcysteine, and Riluzole Robert Hudak, M.D. Associate Professor of Psychiatry University of Pittsburgh School of Medicine
- 2. Snorrason, I., Belleau, E. L., & Woods, D. W. (2012). How related are hair pulling disorder (trichotillomania) and skin picking disorder? A review of evidence for comorbidity, similarities and shared etiology. Clinical Psychology Review, 32(7), 618-629. Medication Treatments for BFRBs Medications Used Results Fluoxetine • Not effective Sertraline • Only mild effect prior to addition of CBT Clomipramine • Superior to desipramine Escitalopram • Mildly more effective than placebo • Somewhat effective
- 3. • SSRIs have not been found to be efficacious in single trials, but meta-analyses are more positive • Clomipramine is shown to be better than placebo and somewhat better than SSRIs Medication Treatments for BFRBs Farhat, L. C., Olfson, E., Nasir, M., Levine, J. L., Li, F., Miguel, E. C., & Bloch, M. H. (2020). Pharmacological and behavioral treatment for trichotillomania: An updated systematic review with meta‐analysis. Depression and Anxiety, 37(8), 715-727
- 4. • SSRIs analyses have shown mixed results • SSRIs are still first-line medications Medication Treatments for BFRBs Farhat, L. C., Olfson, E., Nasir, M., Levine, J. L., Li, F., Miguel, E. C., & Bloch, M. H. (2020). Pharmacological and behavioral treatment for trichotillomania: An updated systematic review with meta‐analysis. Depression and Anxiety, 37(8), 715-727 • All of the SSRIs are considered equivalent, and OCD dosing is always preferred
- 5. Grant, J. E., Odlaug, B. L., & Won Kim, S. (2009). N-acetylcysteine, a glutamate modulator, in the treatment of trichotillomania. Archives of General Psychiatry, 66(7), 756. N-Acetylcysteine for BFRBs An amino acid available over the counter Releases glutamate into the extrasynaptic space Stimulates inhibitory glutamate receptors Reduces synaptic release of glutamate
- 6. - Grant, J. E., Odlaug, B. L., & Won Kim, S. (2009). N-acetylcysteine, a glutamate modulator, in the treatment of trichotillomania. Archives of General Psychiatry, 66(7), 756. - Bloch, M. H., Panza, K. E., Grant, J. E., Pittenger, C., & Leckman, J. F. (2013). N-acetylcysteine in the treatment of pediatric trichotillomania: A randomized, double-blind, placebo-controlled add-on trial. Journal of the American Academy of Child & Adolescent Psychiatry, 52(3), 231-240. - Grant, J. E., Chamberlain, S. R., Redden, S. A., Leppink, E. W., Odlaug, B. L., & Kim, S. W. (2016). N-acetylcysteine in the treatment of excoriation disorder. JAMA Psychiatry, 73(5), 490. N-Acetylcysteine for BFRBs NAC Study Results 50 patients with hair-pulling disorder • 56% improved vs 16% with placebo Children ages 8 to 17 • No improvement vs placebo 66 adults with skin-picking disorder • 47% improved vs 19% with placebo Dose: 1200 mg/day to 2400 mg/day Dose: 1200 mg/day to 3000 mg/day
- 7. - Grant, J. E., Odlaug, B. L., & Won Kim, S. (2009). N-acetylcysteine, a glutamate modulator, in the treatment of trichotillomania. Archives of General Psychiatry, 66(7), 756. - Grant, J. E., Chamberlain, S. R., Redden, S. A., Leppink, E. W., Odlaug, B. L., & Kim, S. W. (2016). N-acetylcysteine in the treatment of excoriation disorder. JAMA Psychiatry, 73(5), 490. • NAC is potentially useful in patients with BFRBs • If no or minimal response to SSRIs, use NAC for augmentation N-Acetylcysteine for BFRBs • Start NAC at 600 mg b.i.d., and increase to 1200 mg b.i.d. if needed • No long-term evidence with NAC, but it is thought to be mostly safe
- 8. Other Medications for BFRBs Farhat, L. C., Olfson, E., Nasir, M., Levine, J. L., Li, F., Miguel, E. C., & Bloch, M. H. (2020). Pharmacological and behavioral treatment for trichotillomania: An updated systematic review with meta‐analysis. Depression and Anxiety, 37(8), 715-727 Medications Used Comments Riluzole • Strong efficacy in OCD Naltrexone • No difference from placebo Lamotrigine • Mixed results • Effective in case series • Not recommended • Not recommended Topiramate • Positive case series • Significant side effects • Not recommended
- 9. - Farhat, L. C., Olfson, E., Nasir, M., Levine, J. L., Li, F., Miguel, E. C., & Bloch, M. H. (2020). Pharmacological and behavioral treatment for trichotillomania: An updated systematic review with meta‐analysis. Depression and Anxiety, 37(8), 715-727 - Van Ameringen, M., Mancini, C., Patterson, B., Bennett, M., & Oakman, J. (2010). A randomized, double-blind, placebo- controlled trial of Olanzapine in the treatment of trichotillomania. The Journal of Clinical Psychiatry, 71(10), 1336-1343. Antipsychotics for BFRBs • Very little data for the use of antipsychotics • Most antipsychotics are not recommended • Olanzapine 10 mg/day: One positive trial • If there is a failed trial of SSRIs and NAC, use olanzapine as second-line augmentation
- 10. Farhat, L. C., Olfson, E., Nasir, M., Levine, J. L., Li, F., Miguel, E. C., & Bloch, M. H. (2020). Pharmacological and behavioral treatment for trichotillomania: An updated systematic review with meta‐analysis. Depression and Anxiety, 37(8), 715-727 Other Treatments for BFRBs Treatments Used Comments Dronabinol • Effective in 1 case series Methylphenidate • Can be used to treat ADHD without increasing hair-pulling disorder symptoms Anterior cingulotomy • Successful in the most severe cases Deep brain stimulation • Not recommended
- 11. Medication Treatment for BFRBs Farhat, L. C., Olfson, E., Nasir, M., Levine, J. L., Li, F., Miguel, E. C., & Bloch, M. H. (2020). Pharmacological and behavioral treatment for trichotillomania: An updated systematic review with meta‐analysis. Depression and Anxiety, 37(8), 715-727 SSRIs are the first line NAC is a first-line augmentation Olanzapine is a second-line augmentation
- 12. • SSRIs and clomipramine are first-line medications for BFRBs. • Use OCD doses for the treatment of BFRBs. • NAC can be used in adults to augment SSRIs or as stand-alone treatment. Key Points
- 13. • Naltrexone, antipsychotics, and lamotrigine have little or no benefit and are not recommended. • Olanzapine can be considered a second-line augmentation. Key Points
- 14. Next Presentation Case Vignette Solution: Treating Mr. J. and Takeaway Points
Editor's Notes
- So video 7. Pharmacologic Treatment of Hair Pulling and Skin Picking Disorders: SSRIs, N-acetylcysteine and Riluzole.
- So medication treatment. So important to note that a treatment for one BFRB can be generalized to the other BFRBs. So if one study is done in hair pulling disorder, you can pretty much take that study and apply it to someone with skin picking disorder or any other specified OCRD that's a BFRB as well. Now, there have been multiple trials of fluoxetine. It's not been found to be effective. Sertraline was studied, only found to have a mild effect prior to addition of CBT. Clomipramine has been studied. Clomipramine is superior to desipramine in treatment but really only mildly more effective than placebo. So clomipramine was one SSRI-like medication. Clomipramine is a tricyclic of course that acts as an SSRI. It's the one SSRI that was found to be somewhat superior to placebo but again only mildly. Other studies. Escitalopram was done as an open label study. It was found to be somewhat effective. *References* Snorrason, I., Belleau, E. L., & Woods, D. W. (2012). How related are hair pulling disorder (trichotillomania) and skin picking disorder? A review of evidence for comorbidity, similarities and shared etiology. Clinical Psychology Review, 32(7), 618-629.
- So what's happened is with most of the SSRIs, they've not really been found to be very efficacious in single stand-alone trials. However, there have been meta-analyses done. And when you pool all the studies together, the results are much more positive. And it does seem that in meta-analysis that the SSRIs do separate out at that point. There have been some meta-analyses where clomipramine is shown to be better than placebo and maybe somewhat better than the SSRIs. *References* Farhat, L. C., Olfson, E., Nasir, M., Levine, J. L., Li, F., Miguel, E. C., & Bloch, M. H. (2020). Pharmacological and behavioral treatment for trichotillomania: An updated systematic review with meta‐analysis. Depression and Anxiety, 37(8), 715-727
- Note that there have been some analyses that have shown that SSRIs do not work. There have been some analyses that show that they do work. At this time, my recommendation is that still we use SSRIs in these patients and that the SSRIs are first-line medications in accordance with usual OCD treatment protocol. Again, all the SSRIs are considered equivalent with BFRBs. And OCD dosing is always preferred in these cases. There have been some other studies that have been done with other medications. *References* Farhat, L. C., Olfson, E., Nasir, M., Levine, J. L., Li, F., Miguel, E. C., & Bloch, M. H. (2020). Pharmacological and behavioral treatment for trichotillomania: An updated systematic review with meta‐analysis. Depression and Anxiety, 37(8), 715-727
- One of the biggest bombshells has been N-acetylcysteine, otherwise known as NAC. NAC is an amino acid that is available over the counter. You can buy it in many health food stores. It causes glial cells to release glutamate into the extrasynaptic space. There, what it does is it stimulates inhibitory glutamate receptors which reduces synaptic release of glutamate. *References* Grant, J. E., Odlaug, B. L., & Won Kim, S. (2009). N-acetylcysteine, a glutamate modulator, in the treatment of trichotillomania. Archives of General Psychiatry, 66(7), 756.
- So NAC was studied with 50 patients with hair pulling disorder at dosage ranging between 1200 and 2400 mg a day. It was noticed that 56% improved very much versus only 16% improving with placebo. And that's a pretty significant result. There was a repeat study that was done in 2013 with a very similar design. It was done in children ages 8 to 17. It should be noted that there was no improvement versus placebo in that cohort. I think the big takeaway home point with that is that children are not little adults. And just because a medication works in children or adults, it doesn't mean it's going to work in the opposite population. And especially meds that work in adults do not always work in children. So there was a second NAC study that was done in 66 adults with skin picking disorder. The dosage ranged between 1200 and 3000 mg a day. So a little higher on the top end. And 47% improved versus 19% on placebo. So the results were very, very similar to the first NAC study with adults. *References* Grant, J. E., Odlaug, B. L., & Won Kim, S. (2009). N-acetylcysteine, a glutamate modulator, in the treatment of trichotillomania. Archives of General Psychiatry, 66(7), 756. Bloch, M. H., Panza, K. E., Grant, J. E., Pittenger, C., & Leckman, J. F. (2013). N-acetylcysteine in the treatment of pediatric trichotillomania: A randomized, double-blind, placebo-controlled add-on trial. Journal of the American Academy of Child & Adolescent Psychiatry, 52(3), 231-240. Grant, J. E., Chamberlain, S. R., Redden, S. A., Leppink, E. W., Odlaug, B. L., & Kim, S. W. (2016). N-acetylcysteine in the treatment of excoriation disorder. JAMA Psychiatry, 73(5), 490.
- So therefore, I think that NAC is certainly a medication that is potentially useful in patients with BFRBs and may be something that has been a bit of a game changer with this in the sense that it's certainly gotten a lot of popularity. I still do recommend that since there are no formal consensus guidelines on what's first-line treatment, NAC or SSRIs, I do recommend that patients still follow typical OCD protocol, that patients should be placed on SSRIs first. However, the difference with that being if the patient does not respond or only minimally responds to the SSRI, the first logical augmentation choice should be NAC at that point. NAC is usually started at 600 mg b.i.d. You can increase to 1200 b.i.d. if needed. Also, please note that the studies have all been short term so there is no long-term evidence with NAC as there is with SSRIs. And there isn't a lot of long-term experience with NAC except clinically as there is with SSRIs. However, no side effects have been reported and it is thought to be mostly safe. Again, because it's something that's over the counter and because there are multiple manufacturers, there's no guarantee that someone gets what they're buying over the counter, that they're getting what they're actually paying for. Again, it's another reason why I always still recommend the SSRIs are first-line treatment for BFRBs and NAC being a secondary augmentation if needed. *References* Grant, J. E., Odlaug, B. L., & Won Kim, S. (2009). N-acetylcysteine, a glutamate modulator, in the treatment of trichotillomania. Archives of General Psychiatry, 66(7), 756. Grant, J. E., Chamberlain, S. R., Redden, S. A., Leppink, E. W., Odlaug, B. L., & Kim, S. W. (2016). N-acetylcysteine in the treatment of excoriation disorder. JAMA Psychiatry, 73(5), 490.
- Other medications. Riluzole is a medication that has been approved for ALS but is shown to have strong efficacy in OCD. It has been effective in case series. Now, naltrexone has been used in the past due to perceived similarities with substance abuse disorders. People are thinking, well naltrexone works for substance abuse disorders, BFRBs kind of act like a substance use disorder. Naltrexone did not separate from placebo. It's not recommended in these patients. Lamotrigine, at best mixed results, not recommended. Topiramate has been studied. There has been a positive case series. However, significant side effects with this medication again makes this something that is not recommended at this time. *References* Farhat, L. C., Olfson, E., Nasir, M., Levine, J. L., Li, F., Miguel, E. C., & Bloch, M. H. (2020). Pharmacological and behavioral treatment for trichotillomania: An updated systematic review with meta‐analysis. Depression and Anxiety, 37(8), 715-727
- Now, there is very little data for the use of antipsychotics and most of it is mixed or open label trials or case series. And therefore, most of the antipsychotics which are often commonly and typically used in BFRBs are not recommended. There is one exception to that. There was one positive double-blind, placebo-controlled trial with olanzapine used at 10 mg daily. As a result, with these BFRBs, if someone has failed SSRIs and if they have failed NAC, I will recommend that they use olanzapine as a second-line augmentation then at that time. *References* Farhat, L. C., Olfson, E., Nasir, M., Levine, J. L., Li, F., Miguel, E. C., & Bloch, M. H. (2020). Pharmacological and behavioral treatment for trichotillomania: An updated systematic review with meta‐analysis. Depression and Anxiety, 37(8), 715-727 Van Ameringen, M., Mancini, C., Patterson, B., Bennett, M., & Oakman, J. (2010). A randomized, double-blind, placebo-controlled trial of Olanzapine in the treatment of trichotillomania. The Journal of Clinical Psychiatry, 71(10), 1336-1343.
- Other medications. Dronabinol has been shown to be effective in one case series. Methylphenidate can be used to treat ADHD without increasing hair pulling disorder symptoms. There are always some concerns with people using stimulants. It can make these symptoms worse. That may not be the case. There are case reports that anterior cingulotomy had been successful in the most severe of these patients. Usually, some surgical interventions such as deep brain stimulation is not recommended because of course that creates another wound. And so cingulotomies tend to be what is recommended. *References* Farhat, L. C., Olfson, E., Nasir, M., Levine, J. L., Li, F., Miguel, E. C., & Bloch, M. H. (2020). Pharmacological and behavioral treatment for trichotillomania: An updated systematic review with meta‐analysis. Depression and Anxiety, 37(8), 715-727
- If I can review again, SSRIs tend to be the first line. NAC I think makes a good augmentation. Olanzapine is a good secondary augmentation. *References* Farhat, L. C., Olfson, E., Nasir, M., Levine, J. L., Li, F., Miguel, E. C., & Bloch, M. H. (2020). Pharmacological and behavioral treatment for trichotillomania: An updated systematic review with meta‐analysis. Depression and Anxiety, 37(8), 715-727
- So the key points. As of this time, SSRIs as well as clomipramine still should be considered first-line medication treatment for BFRBs. You still should use OCD doses in SSRI pharmacotherapy. So for example, doses like 400 mg of sertraline a day. If you're not using 400 mg of sertraline, you're not using sertraline. NAC is a glutamatergic agent. It has been shown to work very well in two studies of adults only. So I think it can be used in adults as augmentation to the SSRIs. It can also be used as a stand-alone medication in patients who will not tolerate the SSRIs.
- Commonly, I see naltrexone, antipsychotics and lamotrigine used in this population. They've been shown to have little or no benefit and therefore, not recommended despite their popularity among clinicians. Now, the one exception to that is olanzapine at 10 mg. It was shown to be effective in one study. Therefore, it can be considered second-line augmentation behind NAC. Thank you.