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Botulinum toxin for depression? An idea that's raising some eyebrows: Botulinum toxin injected into forehead muscles has been shown to relieve depressive symptoms.

Psychiatry is experiencing a major paradigm shift. (1) No longer is depression a disease of norepinephrine and serotonin deficiency. Today, we are exploring inflammation, methylation, epigenetics, and neuroplasticity as major players; we are using innovative treatment interventions such as ketamine, magnets, psilocin, anti-inflammatories, and even botulinum toxin.

In 2006, dermatologist Eric Finzi, MD, PhD, reported a case series of 10 depressed patients who were given a single course of botulinum toxin A (BTA, onabotulinumtoxin A) injections in the forehead. (2) After 2 months, 9 out of the 10 patients were no longer depressed. The 10th patient, who reported improvement in symptoms but not remission, was the only patient with bipolar depression.

As a psychiatrist (M.M.) and a dermatologist (J.R.), we conducted a randomized controlled trial (3) to challenge the difficult-to-swallow notion that a cosmetic intervention could help severely depressed patients. After reporting our positive findings and hearing numerous encouraging patient testimonials, we present a favorable review on the treatment of depression using BTA. We also present the top 10 questions we are asked at lectures about this novel treatment.

A deadly toxin used to treat medical conditions

Botulinum toxin is one of the deadliest substance known to man. (4) It was named after the gram-positive bacterium Clostridium botulinum, which causes so-called floppy baby syndrome in infants who eat contaminated honey. Botulinum toxin prevents nerves from releasing acetylcholine, which causes muscle paralysis.

In the wrong hands, botulinum toxin can be exploited for chemical warfare. (4) However, doctors are using it to treat >50 medical conditions, including migraine, cervical dystonia, strabismus, overactive bladder, urinary incontinence, excessive sweating, muscle spasm, and now depression. (5-6) In 2014, BTA was the top cosmetic treatment in the United States, with >3 million procedures performed, generating more than 1 billion dollars in revenue. (7)

The most common site injected with BTA for cosmetic treatments is the glabellar region, which is the area directly above and in between the eyebrows (ie, the lower forehead). The glabella comprises 2 main muscles: the central procerus flanked by a pair of corrugators (Figure). When expressing fear, anger, sadness, or anguish, these muscles contract, causing the appearance of 2 vertical wrinkles, referred to as the "11s." The wrinkles also can form the shape of an upside-down "U," known as the omega sign. (8) BTA prevents contraction of these muscles and therefore prevents the appearance of a furrowed brow. During cosmetic procedures, approximately 20 to 50 units of BTA are spread out over 5 glabellar injection sites. (9) A similar technique is being used in studies of BTA for depression (2-3-10-11) (Figure).

BTA for depression is new to the mental health world but, before psychiatrists caught on, dermatologists were aware that BTA could improve quality of life, (12) reduce negative emotions, (13) and increase feelings of well-being. (14)

The evidence

To date, there have been 2 case series, (2,15) 3 randomized control trials (RCTs), (3,10,11) pooled analysis, (16,17) and 1 meta-analysis (18) looking at botulinum for depression (Table 1, page 52). (2,10,11,15-17) in each trial, a single treatment of BTA (ie, 1 doctor's visit; 29 to 40 units of BTA distributed into 5 glabellar injections sites), was the intervention studied. (2)

The first case series, by Finzi and Wasserman (2) is described above. A second case series, published in 2013, describes 50 female patients, one-half depressed and one-half non-depressed, all of whom received 20 units of BTA into the glabella. (15) At 12 weeks, depression scores in the depressed group had decreased by 54% (14.9 point drop on Beck Depression Inventory [BDI], P < .001) and self-esteem scores had increased significantly. In non-depressed participants, depression scores and self-esteem scores remained constant throughout the 12 weeks.

A pooled analysis reported results of 3 RCTs (16,17) consisting of a total of 134 depressed patients, males and females age 18 to 65 who received BTA (n = 59) or placebo (n = 74) into the glabellar region. At the end of 6 weeks, BDI scores in the depressed group had decreased by 47.4% (14.3 points) compared with a 16.2% decrease (5.1 points) in the placebo group. This corresponds to a 52.5% vs 8.0% response rate and a 42.4% vs 8.0% remission rate, respectively (Table, (1,2,10,11,15-17) page 52). There was no difference between the 2 groups in sex, age, depression severity, and number of antidepressants being taken. Females received 29 units and males received 10 to 11 units more to account for higher muscle mass (Figure, page 46).

Depression as measured by the physician-administered Hamilton Depression Rating Scale (HAM-D) and the Montgomery-Asberg Depression Rating Scale showed similar reduction in overall scores (-45.7% vs -14.6%), response rates (54.2% vs 10.7%) and remission rates (30.5% vs 6.7%) with BTA.

Although these improvements in depression scores do not reach those seen with electroconvulsive therapy, (19,20) they are comparable to placebo-controlled studies of antidepressants. (21,22)

Doesn't this technique work because people who look better, feel better?

Aesthetic improvement alone is unlikely to explain the entire story. A recent study showed that improvement in wrinkle score did not correlate with improvement in mood. (23) Furthermore, some patients in RCTs did not like the cosmetic effects of BTA but still reported feeling less depressed after treatment. (10)

How might it work?

Several theories about the mechanism of action have been proposed:

* The facial feedback hypothesis dates to Charles Darwin in 1872: Facial movements influence emotional states. Numerous studies have confirmed this. Strack et al (24) found that patients asked to smile while reading comics found them to be funnier. Ekman et al (25) found that imitating angry facial expressions made body temperature and heart rate rise. Dialectical behavioral therapy expert Marsha Linehan recognized the importance of modifying facial expressions (from grimacing to smiling) and posture (from clenched fists to open hands) when feeling distressed, because it is hard to feel "willful" when your "mind is going one way and your body is going another." (26) Accordingly, for a person who continuously "looks" depressed or distressed, reducing the anguished facial expression using botulinum toxin might diminish the entwined negative emotions.

* A more pleasant facial expression improves social interactions, which leads to improvement in self-esteem and mood. Social biologists argue that (1) we are attracted to those who have more pleasant facial expressions and (2) we steer clear of those who appear angry or depressed (a negative facial expression, such as a growling dog, is perceived as a threat). Therefore, anyone who looks depressed might have less rewarding interpersonal interactions, which can contribute to a poor mood.

On a similar note, mirror neurons are regions in the brain that are activated by witnessing another person's emotional cues. When our mirror neurons light up, we can feel an observed experience, which is why we often feel nervous around anxious people, or cringe when we see others get hurt, or why we might prefer engaging with people who appear happier. It is possible that, after BTA injection, a person's social connectivity is improved because of a more positive reciprocal firing of mirror neurons.

* BTA leads to direct and indirect neurochemical changes in the brain that can reduce depression. Functional MRI studies have shown that after glabellar BTA injections, the amygdala was less responsive to negative stimuli. (27,28) For example, patients who were treated with BTA and then shown pictures of angry people had an attenuated amygdala response to the photos.

This is an important finding, especially for patients who have been traumatized. After a traumatic event, the amygdala "remembers" what happened, which is good, in some ways (it prevents us from getting into a similar dangerous situation), but bad in others (the traumatized amygdala may falsely perceive a non-threatening stimuli as threatening). A hypervigilant amygdala can lead to an out-of-proportion fear response, depression, and anxiety. Therefore, quelling an overactive amygdala with BTA could improve emotional dysregulation and posttraumatic disorders.

Many of our patients reported that, after BTA injection, "traumatic events didn't feel as traumatizing," as one said. The emotional pain and rumination that often follow a life stressor "does not overstay its welcome" and patients are able to "move on" more quickly.

It is unknown why the amygdala is quieted after BTA; researchers hypothesize that BTA suppresses facial feedback signals from the forehead branch of the trigeminal nerve to the brain. Another hypothesis is that BTA is directly transported by the trigeminal nerve into the brain and exerts central pharmacological effects on the amygdala. (29) This theory has only been studied in rat models. (30)

When does it start working? How long does it last?

From what we know, BTA for depression could start working as early as 2 weeks and could last as long as 6 months. In one RCT, the earliest follow-up was 2 weeks, (10) at which time the depressed patients had responded to botulinum toxin (P [less than or equal to] .05). In the other 2 controlled trials, the earliest follow-up was 3 weeks, at which time a more robust response was seen (P < .001). Aesthetically, BTA usually lasts 3 months. It is unclear how long the antidepressant effects last but, in the longest trial, (3) depression symptoms continued to improve at 6 months, after cosmetic effects had worn off.

These findings raise a series of questions:

* Do mood effects outlast cosmetic effects? If so, why?

* Does botulinum toxin start to work sooner than 2 weeks?

* Will adherence improve if a patient has to be treated only every 6 months?

In our clinical experience, depressed patients who responded to BTA injection report a slow resurfacing of depressive symptoms 4 to 6 months after treatment, at which point they usually return for "maintenance treatment" (same dosing, same injection configuration).

Will psychiatrists administer the treatment?

Amy physician or physician extender can, when properly trained, inject BTA. The question is: Do psychiatrists want to?

Administrating botulinum toxin requires more labor and preparation than prescribing a drug (Table 2, (31) page 54) and requires placing hands on patients. Depending on the type of psychiatric practice, this may be a "deal-breaker" for some providers, such as those in a psychoanalytic practice who might worry about boundaries.

As a basis for comparison, despite several indications for BTA for headache and neurologic conditions, few neurologists have added botulinum toxin to their practice. Dermatologists who are comfortable seeing psychiatric patients or family practitioners, who are already set up for injection procedures, could become custodians of this intervention.

Which patients are candidates for the treatment?

Patients with anxious or agitated depression might be ideal candidates for BTA injection. A recent study looked at predictors of response: Patients with a high agitation score (as measured on item 9 of the HAM-D) were more likely to respond, with a sensitivity of 100%, a specificity of 56%, and an overall precision of 78%. (32) So far, no other predictors of response have been clearly identified. Higher baseline wrinkle scores do not predict better response. (23) Sex and age do not have any predictive value. The treatment appears to be equally effective in males and females; because only a handful of males have been treated (n = 14), however, these patients need to be studied further.

Is botulinum toxin better as monotherapy or augmentation strategy?

So far, it appears to be equally effective as monotherapy or augmentation strategy, (16) but more studies are needed.

How expensive is it?

Estimates of patient cost include the cost of the product and the professional fee for injection. As a point of reference, for cosmetic purposes, depending on practice location, dermatologists charge $11 to $20 per unit of BTA. Therefore, 1 treatment of BTA for depression (29 to 40 units) can cost a patient $319 to $800.

When treating a patient with BTA for medical indications, such as tension headache, insurance often reimburses the physician for the BTA at cost (paid with a J code: J0585) and pay an injection fee (a procedure code) of $150 to $200. A recent analysis of cost-effectiveness estimated that BTA for depression would cost a patient $1,200 to $1,600 annually. (33) Compared with the price of branded medications (eg, $500 to $2,000 annually) (33) plus weekly psychotherapy (eg, $2,000 to $5,000 annually), BTA may be a cost-effective option for patients who do not respond to conventional treatments. Of course, for patients who tolerate and respond to generic medications or have a therapist who charges on a sliding scale, BTA is not the most cost-effective option.

What about injecting other areas of the face?

We've thought about it but haven't tried it.

There are several muscles around the mouth that allow us to smile and frown. BTA injections in the depressor anguli oris, a muscle around the mouth that is largely responsible for frowning, could treat depression. However, if the mechanism of action is via amygdala desensitization through the trigeminal nerve, treating mouth frown muscles might not work.

Is it safe?

BTA in the glabella has an exceptionally good safety profile. (9,31,34) Adverse reactions, which include eyelid droop, pain, bruising, and redness at the injection site, are minor and temporary. (9) In addition, BTA has few drug-drug interactions. The biggest complaint for most patients is discomfort upon injection, which often is described as feeling like "an ant bite."

In the pooled analysis of RCTs, apart from local irritation immediately after injection, temporary headache was the only relevant, and possibly treatment-related, adverse event. Headache occurred in 13.6% (n = 8) of the BTA group and 9.3% (n = 7) of the placebo group (P = .44). Compared with antidepressants such as citalopram, where approximately 38.6% of patients report a moderate or severe side-effect burden, (21) BTA is well tolerated.

Are other studies underway?

Larger studies are being conducted, (35) mainly to confirm what pilot studies have shown. It would be interesting to discover other predictors of response and if different dosing and injection configurations could strengthen the response rate and extend the duration of effect.

Because of the cosmetic effects of BTA, further studies are needed to address the problem of blinding. In earlier studies, raters were blinded during appointments because patients wore surgical caps that covered their glabellar region. (3,10) Patients did not know their treatment intervention, but 52% to 90% of patients guessed correctly. (3,10,11) Although unblinding is a common problem in "blinded" trials in which some researchers have reported >75% of participants and raters guessed the intervention correctly, (36) it is a particularly sensitive area in studies that involve a change in appearance because it is almost impossible to prevent someone from looking in a mirror.

Summing up

Botulinum toxin for depression is not ready for prime time. The FDA has not approved its use for psychiatric indications, and Medicare and commercial insurance do not reimburse for this procedure as a treatment for depression. Patients who request BTA for depression must be informed that this use is off-label.

For now, we recommend psychotherapy or medication management, or both, for most patients with major depression. In addition, until larger studies are done, we recommend that patients who are interested in BTA for depression use it as an add-on to conventional treatment. However, if larger studies replicate the findings of the smaller studies we have described, botulinum toxin could become a novel therapeutic agent in the fight against depression.

Clinical Point

BTA prevents contraction of muscles in the glabellar region, thus preventing the appearance of a furrowed brow

Clinical Point

A recent study showed that improvement in wrinkle score did not correlate with improvement in mood

Clinical Point

It is possible that, after BTA, a person's social connectivity is improved because of a more positive reciprocal firing of mirror neurons

Clinical Point

Depressed patients who responded to BTA injection report a slow resurfacing of depressive symptoms 4 to 6 months after treatment

Clinical Point

Patients with anxious or agitated depression might be ideal candidates for BTA injection

Clinical Point

Apart from local irritation, temporary headache was the only relevant, and possibly the only treatment-related, adverse event of BTA

Clinical Point

We recommend that patients who are interested in BTA for depression use it as an add-on to conventional treatment

Disclosures

In July 2011, Dr. Magid received a young investigator award from the Brain and Behavior Research Foundation for her study on treating depression using botulinum toxin (Grant number 17648). In November 2012, after completion and as a result of the study on treating depression using botulinum toxin, Dr. Magid became a consultant with Allergan to discuss study findings. In September 2015, Dr. Magid became a speaker for IPSEN Innovation. Dr. Reichenberg is married to Dr. Magid. Dr. Reichenberg has no other conflicts of interest to disclose.

Related Resources

* Wollmer MA, Magid M, Kruger THC. Botulinum toxin treatment in depression. In: Bewley A, Taylor RE, Reichenberg JS, et al, eds. Practical psychodermatology. Hoboken, NJ: John Wiley & Sons; 2014:216-219.

* Botox for depression, www.botoxfordepression.com.

* Botox and depression, www.botoxanddepression.com.

Drug Brand Names

Botulinum toxin A * Botox Citalopram * Celexa

Acknowledgments

We thank the Brain and Behavior Research Foundation for granting Dr. Magid a young investigator award and for continuing to invest in innovative research ideas. We thank Dr. Eric Finzi, MD, PhD, Axel Wollmer, MD, and Tillmann Kruger, MD, for their continued collaboration in this area of research.

Michelle Magid, MD

Clinical Assistant Professor Texas A&M Health Science Center Round Rock, Texas Clinical Assistant Professor University of Texas Galveston, Texas Adjunct Faculty Department of Psychiatry

University of Texas Dell Medical School at Seton Family of Hospitals Austin, Texas

Jason Reichenberg, MD Associate Professor Department of Dermatology

University of Texas Dell Medical School at Seton Family of Hospitals Austin, Texas

References

(1.) Nasrallah HA. 10 Recent paradigm shifts in the neurobiology and treatment of depression. Current Psychiatry. 2015;14(2):10-13.

(2.) Finzi E, Wasserman E. Treatment of depression with botulinum toxin A: a case series. Dermatol Surg. 2006; 32(5):645-649; discussion 649-650.

(3.) Magid M, Reichenberg JS, Poth PE, et al. Treatment of major depressive disorder using botulinum toxin A: a 24-week randomized, double-blind, placebo-controlled study. J Clin Psychiatry. 2014;75(8):837-844.

(4.) Koussoulakos S. Botulinum neurotoxin: the ugly duckling. Eur Neurol. 2008;61(6):331-342.

(5.) Chen S. Clinical uses of botulinum neurotoxins: current indications, limitations and future developments. Toxins (Basel). 2012;4(10):913-939.

(6.) Bhidayasiri R, Truong DD. Expanding use of botulinum toxin. J Neurol Sd. 2005;235(l-l):l-9.

(7.) Cosmetic surgery national data bank statistics. American Society for Asethetic Plastic Surgery. http://www.surgery.org/sites/default/files/2014-Stats.pdf. Published 2014. Accessed May 30, 2015.

(8.) Shorter E. Darwin's contribution to psychiatry. Br J Psychiatry. 2009;195(6):473-474.

(9.) Winter L, Spiegel J. Botulinum toxin type-A in the treatment of glabellar lines. Clin Cosmet Investig Dermatol. 2009;3:1-4.

(10.) Wollmer MA, de Boer C, Kalak N, et al. Facing depression with botulinum toxin: a randomized controlled trial. J Psychiatr Res. 2012;46(5):574-581.

(11.) Finzi E, Rosenthal NE. Treatment of depression with onabotulinumtoxinA: a randomized, double-blind, placebo controlled trial. J Psychiatr Res. 2014;52:1-6.

(12.) Hexsel D, Brum C, Porto MD, et al. Quality of life and satisfaction of patients after full-face injections of abobotulinum toxin type A: a randomized, phase IV clinical trial. J Drugs Dermatol. 2013;12(12):1363-1367.

(13.) Lewis MB, Bowler PJ. Botulinum toxin cosmetic therapy correlates with a more positive mood. J Cosmet Dermatol. 2009;8(l):24-26.

(14.) Sommer B, Zschocke I, Bergfeld D, et al. Satisfaction of patients after treatment with botulinum toxin for dynamic facial lines. Dermatol Surg. 2003;29(5):456-460.

(15.) Hexsel D, Brum C, Siega C, et al. Evaluation of self-esteem and depression symptoms in depressed and nondepressed subjects treated with onabotulinumtoxina for glabellar lines. Dermatol Suig. 2013;39(7):1088-1096.

(16.) Magid M, Reichenberg JS, Finzi E, et al. Treating depression with botulinum toxin: update and meta-analysis from clinic trials. Paper presented at: XVI World Congress of Psychiatry; September 14-18, 2014; Madrid, Spain.

(17.) Magid M, Finzi E, Kruger TH, et al. Treating depression with botulinum toxin: a pooled analysis of randomized controlled trials. Pharmacopsychiatry. 2015;48(6):205-210.

(18.) Parsaik A, Mascarenhas S, Hashmi A, et al. Role of botulinum toxin in depression: a systematic review and meta-analysis. J Psychiatr Pract. In press.

(19.) Scott Al, ed. The ECT handbook, 2nd ed. The third report of the Royal College of Psychiatrists' Special Committee of ECT. London, United Kingdom: The Royal College of Psychiatrists; 2005.

(20.) Ren J, Li H, Palaniyappan L, et al. Repetitive transcranial magnetic stimulation versus electroconvulsive therapy for major depression: a systematic review and meta-analysis. Prog Neuropsychopharmacol Biol Psychiatry. 2014;51:181-189.

(21.) Trivedi MH, Rush AJ, Wisniewski SR, et al; STAR'D Study Team. Evaluation of outcomes with citalopram for depression using measurement-based care in STAR* D: implications for clinical practice. Am J Psychiatry. 2006; 163(1):28-40.

(22.) Gibbons RD, Hur K, Brown CH, et al. Benefits from antidepressants: synthesis of 6-week patient-level outcomes from double-blind placebo-controlled randomized trials of fluoxetine and venlafaxine. Arch Gen Psychiatry. 2012; 69(6)572-579.

(23.) Reichenberg JS, Magid M, Keeling B. Botulinum toxin for depression: does the presence of rhytids predict response? Presented at: Texas Dermatology Society; May 2015; Bastrop, Texas.

(24.) Strack F, Martin LL, Stepper S. Inhibiting and facilitating conditions of the human smile: a nonobtrusive test of the facial feedback hypothesis. J Pers Soc Psychol. 198854(5):768-777.

(25.) Ekman P, Levenson RW, Friesen WV. Autonomic nervous system activity distinguishes among emotions. Science. 1983;221(4616):1208-1210.

(26.) Linehan MM. DBT skills training manual, 2nd ed. New York, NY: Guilford Publications; 2014.

(27.) Hennenlotter A, Dresel C, Castrop F, et al. The link between facial feedback and neural activity within central circuitries of emotion--new insights from botulinum toxin-induced denervation of frown muscles. Cereb Cortex. 2009;19(3): 537-542.

(28.) Kim MJ, Neta M, Davis FC, et al. Botulinum toxin-induced facial muscle paralysis affects amygdala responses to the perception of emotional expressions: preliminary findings from an A-B-A design. Biol Mood Anxiety Disord. 2014;4:11.

(29.) Mazzocchio R, Caleo M. More than at the neuromuscular synapse: actions of botulinum neurotoxin A in the central nervous system. Neuroscientist. 2015;21(1):44-61.

(30.) Antonucd F, Rossi C, Gianfranceschi L, et al. Long-distance retrograde effects of botulinum neurotoxin A. J Neurosci. 2008;28(14):3689-3696.

(31.) U.S. Food and Drug Administration. Medication guide: botox. http://www.fda.gov/downloads/drugs/drugsafety/ucml76360.pdf. Updated September 2013. Accessed June 7, 2015.

(32.) Wollmer MA, Kalak N, Jung S, et al. Agitation predicts response of depression to botulinum toxin treatment in a randomized controlled trial. Front Psychiatry. 20145:36.

(33.) Beer K. Cost effectiveness of botulinum toxins for the treatment of depression: preliminary observations. J Drugs Dermatol. 2010,-9(l):27-30.

(34.) Brin MF, Boodhoo TI, Pogoda JM, et al. Safety and tolerability of onabotulinumtoxinA in the treatment of facial lines: a meta-analysis of individual patient data from global clinical registration studies in 1678 participants. J Am Acad Dermatol. 2009;61(6):961-970.el-ll.

(35.) Botulinum toxin and depression. ClinicalTrials.gov. https://clinicaltrials.gov/ct2/results?term=botulinum+toxin+and+ depression&Search=Search. Accessed June 1, 2015.

(36.) Rabkin JG, Markowitz JS, Stewart J, et al. How blind is blind? Assessment of patient and doctor medication guesses in a placebo-controlled trial of imipramine and phenelzine. Psychiatry Res. 1986;19(l):75-86.

Bottom Line

In pilot studies, botulinum toxin A (BTA) has shown efficacy in improving symptoms of depression. Although considered safe, BTA is not FDA-approved for psychiatric indications, and Medicare and commercial insurance do not reimburse for this procedure for depression. Larger studies are underway to determine if this novel treatment can be introduced into practice.

Table 1
Studies on treating major depressive disorder
using botulinum toxin A

Study                      Design

Finzi and                  Case series; 10 depressed
Wasserman 2006 (2)         females age 18 to 65, all
                           receiving BTA

Wollmer et al, 2012 (10)   RCT; 30 depressed males
                           and females age 25 to 64,15
                           receiving BTA and 15 receiving
                           placebo

Hexsel et al, 2013 (15)    Case series; 50 females age 25
                           to 60,25 depressed and 25 non-
                           depressed, all receiving BTA

Finzi et al, 2014 (11)     RCT; 74 depressed males
                           and females, 33 receiving BTA
                           and 41 receiving placebo

Magid et al, 2014 (16)     Crossover RCT; 30 depressed
                           males and females, 11 receiving
                           BTA and 19 receiving placebo.
                           Groups switched treatment
                           halfway through study

Magid et al, 2015 (17)     Pooled analysis; 134 depressed
                           males and females, 59 receiving
                           BTA and 75 receiving placebo

                           Were patients                Week for
                           taking an         Length     reporting
Study                      antidepressant?   of trial   results

Finzi and                  No: 5             8 weeks    Week 6
Wasserman 2006 (2)         Yes: 5

Wollmer et al, 2012 (10)   No: 1             16 weeks   Week 6
                           Yes: 29

Hexsel et al, 2013 (15)    Yes: 25           12 weeks   Week 12
                           No: 25
                           All depressed
                           patients were
                           taking an
                           antidepressant

Finzi et al, 2014 (11)     No: 43            6 weeks    Week 6
                           Yes: 31

Magid et al, 2014 (16)     No: 4             24 weeks   Week 6,
                           Yes: 26                      Week 18
                                                        (crossover at
                                                        week 12)

Magid et al, 2015 (17)     No: 48            Variable   Week 6
                           Yes: 86

Study                      Comments

Finzi and                  Depressed patients treated with BTA
Wasserman 2006 (2)         experienced a 90% BDI-II response rate
                           and a 73.6% reduction in BDI-II scores

Wollmer et al, 2012 (10)   Depressed patients treated with BTA vs
                           placebo experienced a -47% vs -9% change
                           in score (P = .002), a 60% vs 13%
                           response rate (P = .02), and a 33% vs
                           13% remission rate (P > .05) as measured
                           by HAMD-17 Depressed patients treated
                           with BTA experienced a 54.4% reduction
                           in BDI scores in (P < .001). Self-esteem
                           scores also significantly improved.
                           Nondepressed patients' self-esteem and
                           depression scores did not significantly
                           change

Hexsel et al, 2013 (15)    Depressed patients treated with BTA vs
                           placebo experienced a -55% vs -21%
                           change in score (P < .001), a 61 % vs
                           12% response rate (P < .0001), and a 48%
                           vs 12% remission rate (P < .001) as
                           measured BDI-II

Finzi et al, 2014 (11)     Depressed patients treated with BTA vs
                           placebo experienced a -42% vs -15%
                           change in score (P < .0001), a 45% vs 5%
                           response rate (P = .0067), and a 27% vs
                           5% remission rate (P = .09) as measured
                           BDI. Depressed patients treated with BTA
                           continued to improve throughout the 24
Magidetal, 2015 (17)       weeks, even when cosmetic effects of BTA
                           wore off When placebo patients were
                           switched to BTA, they also showed a
                           statistically significant improvement

Magid et al, 2014 (16)     Depressed patients treated with BTA vs
                           placebo experienced a -47% vs -16%
                           change in score (P < .0001), a 53% vs 8%
                           response rate (P < .0001), and a 42% vs
                           8% remission rate (P < .0001)

BDI-II: Beck Depression Inventory-II; BTA: botulinum toxin A; HAMD-17:
Hamilton Depression Rating Scale-17; RCT: randomized controlled trial

Table 2
Starting a botulinum toxin
for depression practice can
be daunting

Obtain certification on proper injection
technique; get training on how to reconstitute
BTA powder into the active form

Set up an account with a reputable supplier
for BTA delivery

Set up an account to obtain ancillary supplies,
including syringes, alcohol pads, gauzes,
gloves, and ice packs

Buy a medical-grade refrigerator with a lock
to store the BTA product; create a protocol
to ensure that the refrigerator stays at the
appropriate temperature

Obtain a sharps box to dispose of used
needles that meets health and safety regulation
standards; create a system to ensure the box is
emptied appropriately when full

Create patient consent forms and new note
templates for BTA visits

Create different appointment slots for BTA
procedures; you could need more or less
time than a typical patient visit, depending
on your skill. Schedule patients close enough
together to ensure you use all BTA before it
loses effectiveness and needs to be discarded
(FDA recommends using within 24 hours of
reconstitution (31))

Addition of a new procedure might affect your
malpractice insurance; check with your carrier
on rate adjustments

Medical procedures may require you to update
your billing system or hire extra medical staff to
help assist and coordinate care, or both

BTA: botulinum toxin A
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Date:Nov 1, 2015
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