SCOTTSDALE, Arizona — Botulinum toxin type A (BT), commonly known as Botox, may play a role in the treatment of bipolar depression and social anxiety disorder, preliminary research suggests.
In two small case series, injecting BT into the glabellar region of the face — the area between the eyebrows and above the nose — reduced symptoms of treatment-resistant bipolar depression as well as social anxiety.
In the first case series, 4 of 6 individuals with bipolar disorder with moderate to severe depressive episodes experienced sustained remission following treatment with BT.
The remaining two patients experienced a reduction in depressive symptoms, and one was able to avoid a second round of electroconvulsive therapy.
In the second case series, 3 of 6 women with long-standing, treatment-resistant social anxiety disorder experienced sustained remission following treatment with BT. The remainder experienced a reduction in social anxiety symptoms.
“I credit William James and Charles Darwin for giving me the idea. The whole reason for starting this was the concept of what I call emotional proprioception — facial expressions provide information to the brain about how good or how bad things are out there, and they help regulate mood. The original ideas come from James and Darwin. I’ve just updated them to the 21st century,” study investigator Eric Finzi, MD, PhD, George Washington University School of Medicine, Washington, DC, told Medscape Medical News.
The findings were presented here at the American Society of Clinical Psychopharmacology (ASCP) 2019 annual meeting.
Using Muscles to Treat Mood
Finzi said he began studying BT for depression in 2003 and authored a case series in 2006.
The results were replicated by three independent groups. The use of BT for the treatment of major depressive disorder is currently being studied in phase 3 clinical trials, he noted.
“Afferent nerve fibers appear to relay emotional information to the brain on a moment-to-moment basis, signaling our emotional state. We propose that the brain utilizes facial muscle expression to provide such emotional proprioception.
“When we paralyze muscle fibers with BT, this may signal to the trigeminal nerve endings, possibly those involved in registering pain or muscle tension, a relief of physical stress, resulting in decreased emotional stress. It’s kind of an out-of-the-box concept of using muscles to treat mood. We’re saying that by affecting facial muscles, you’re sending a signal back to the brain,” Finzi said.
Finzi reasoned that if BT was effective for unipolar depression, it would also alleviate depressive symptoms in patients with bipolar disorder.
One woman and five men aged 39 to 87 years who had bipolar depression were injected with 29 to 46 units of onabotulinumtoxin A at five to seven injection points in the glabellar region.
For all six patients, previous and current pharmacologic and psychotherapeutic treatments were insufficient or had been stopped because of side effects.
The Beck Depression Inventory I and II (BDI, BDI II) were used to assess the severity of depression before and after treatment in four cases; the Quick Inventory of Depressive Symptoms Self Report–16 (QIDS SR-16) was used to assess symptoms in one case; and the Montgomery-Åsberg Depression Rating Scale (MADRS) was used in one case.
Most patients’ conditions went into remission, and all showed improvement in depressive symptoms.
In one case, a 49-year-old man with a 3-year depressive episode that was treatment resistant began to improve within 1 week after injection, and his condition went into remission within 4 weeks. Subsequently, he discontinued all other medications.
In another case, a 51-year-old man began to experience improvement 1 week after injection. One month after receiving BT injection, his BDI II score was zero. He has undergone repeat treatments every 3 months, and remission has been maintained for 18 months, Finzi noted.
After discontinuing lithium secondary to kidney side effects, a 55-year-old patient received a BT injection. Within 4 weeks, the patient experienced almost complete remission of depressive symptoms, as measured by the BDI II. However, 10 days later, his frown began to be active again, and his depression returned. He was retreated with a greater dose (48 units), and the results were the same as with the initial treatment.
Table. Depression Scores Before and After Botulinum Toxin Treatment
Patients respond to the injections within a month. However, symptoms reappear after about 3 months, Finzi said.
“Response takes some time. It’s not instantaneous. The other piece of information that strongly suggests that the botulinum toxin is the cause of the remission is that its effect wears off after about 3 months, so the mood is good while the botulinum toxin is working, and then the mood becomes bad again when it wears off,” he said.
In a case series of patients with social anxiety disorder whose symptoms persisted for more than 10 years without remission, six women aged 32 to 61 years received 29 units of BT.
For all but one of the patients, previous or current pharmacologic and psychotherapeutic treatments had either been insufficient to control anxiety or were discontinued because of side effects.
Three of the six patients experienced sustained remission following BT injection. Long-term follow-up indicates that remission has been sustained, without relapse, for more than 1 year.
The remaining three patients experienced some relief, and 5 of the 6 patients have elected to continue treatments to maintain their improvement, Finzi said.
Mechanism Makes Sense
Commenting on the findings for Medscape Medical News, Alan F. Schatzberg, MD, Kenneth T. Norris Jr Professor of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, California, said there are data to indicate that the so-called corrugator response, or furrowing of the brow, is significantly correlated with overactivity of the amygdala response and underactivity of the prefrontal cortex response to negative facial challenges seen on fMRI in healthy persons.
“These functional processes have been reported to be affected by Botox, which appears to increase the prefrontal cortex’s control of the amygdala. Thus, it would not be terribly surprising if the drug helped in social anxiety,” said Schatzberg.
Finzi is a named inventor on patents to treat depression with botulinum toxin and is a coinventor on a patent to treat social anxiety disorder with botulinum toxin. Schatzberg has disclosed no relevant financial relationships.