Novel pharmacological treatments for generalized anxiety disorder: Pediatric considerations

Abstract

Background
Pediatric anxiety disorders such as generalized anxiety disorder (GAD) are common, impairing, and often undertreated. Moreover, many youth do not respond to standard, evidence‐based psychosocial or psychopharmacologic treatment. An increased understanding of the gamma‐aminobutyric acid (GABA) and glutamate neurotransmitter systems has created opportunities for novel intervention development for pediatric GAD.

Methods
This narrative review examines potential candidates for pediatric GAD: eszopiclone, riluzole, eglumegad (LY354740), pimavanserin, agomelatine.

Results
The pharmacology, preclinical data, clinical trial findings and known side effects of eszopiclone, riluzole, eglumegad (LY354740), pimavanserin, agomelatine, are reviewed, particularly with regard to their potential therapeutic relevance to pediatric GAD.

Conclusion
Notwithstanding numerous challenges, some of these agents represent potential candidate drugs for pediatric GAD. Further treatment development studies of agomelatine, eszopiclone, pimavanserin and riluzole for pediatric GAD also have the prospect of informing the understanding of GABAergic and glutamatergic function across development.

Microwave Thermolysis Reduces Generalized and Social Anxiety in Young Adults With Axillary Hyperhidrosis.

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Microwave Thermolysis Reduces Generalized and Social Anxiety in Young Adults With Axillary Hyperhidrosis.

Lasers Surg Med. 2020 Mar 16;:

Authors: Parrish C, Waldbaum B, Coleman D, Blevins C, Rodgers K, Lee B, Ober C, Hudhud L, Cox S, Griffin C, Chew S, Chen B, Brock M

Abstract
BACKGROUND AND OBJECTIVE: Hyperhidrosis (HH) is associated with impairments in quality of life (QOL) and elevated anxiety. Microwave thermolysis is a newer treatment that reduces sweating, yet effects on QOL and emotional symptoms have not been examined. Two treatment sessions are recommended to achieve 80% amelioration of clinical HH. We hypothesized that microwave thermolysis would reduce sweat severity, improve QOL, and reduce anxiety in young adults suffering from axillary HH in a prospective clinical trial.
STUDY DESIGN/MATERIALS AND METHODS: We enrolled 24 young adults (mean age = 23.57 years, 54% female) with elevated scores on the Hyperhidrosis Disease Severity Scale. All participants received one session of microwave thermolysis, and 83% received two sessions. Participants completed measures of sweat severity, QOL, generalized anxiety, social anxiety, social avoidance, and anxious/depressive mood symptoms at baseline; post-first treatment; and following second treatment.
RESULTS: At baseline, all participants had severe sweating; 87.5% had impaired QOL, 75% had elevated social anxiety, 50% with generalized anxiety, 48% with social avoidance, and 38% with anxious/depressed mood. Paired samples t tests indicated significant improvements from baseline to first procedure, including decreased sweating (t(21) = 5.68, P < 0.001), improved QOL (t(23) = 4.97, P < 0.001), and decreased generalized anxiety (t(23) = 8.11, P < 0.001), social anxiety (t(22) = 4.55, P < 0.001), mood symptoms (t(21) = 3.81, P = 0.001), and social avoidance (t(22) = 3.12, P = 0.005). After second treatment, further improvements were noted in sweating (t(18) = 3.28, P = 0.004) and QOL (t(18) = 3.83, P = 0.003), and a marginal trend for generalized anxiety (t(19) = 1.96, P = 0.064).
CONCLUSION: There were significant improvements in sweat severity, skin-specific QOL, generalized anxiety, social anxiety, anxious/depressive symptoms, and social avoidance. The majority of the psychosocial benefit appears to emerge after one treatment of microwave thermolysis, whereas the level of sweat severity and QOL continued to show further improvements after a second treatment. Results would suggest that although two microwave thermolysis sessions are needed for maximal treatment optimization of axillary HH, patients may experience significant benefits in improving psychosocial functioning after just one session. Lasers Surg. Med. © 2020 Wiley Periodicals, Inc.

PMID: 32175622 [PubMed – as supplied by publisher]

Botulinum Toxin: Pharmacology and Injectable Administration for the Treatment of Primary Hyperhidrosis.

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Botulinum Toxin: Pharmacology and Injectable Administration for the Treatment of Primary Hyperhidrosis.

J Am Acad Dermatol. 2019 Dec 04;:

Authors: Nawrocki S, Cha J

Abstract
Hyperhidrosis is a dermatological condition defined by excessive sweating beyond thermoregulatory needs with significant effects on patients’ quality of life. Hyperhidrosis is categorized as primary or secondary: primary hyperhidrosis is mostly focal and idiopathic, whereas secondary hyperhidrosis is commonly generalized and caused by an underlying medical condition or use of medications. Various surgical and nonsurgical therapies exist for primary hyperhidrosis. Although botulinum toxin is one of the deadliest toxins known, when used in small doses, it is one of the most effective therapies for primary hyperhidrosis. Botulinum toxin injections are widely used as a second-line primary hyperhidrosis treatment option, when topical treatment strategies have failed. This article provides an overview of the commercially available botulinum toxin formulations and their applications for the treatment of primary hyperhidrosis.

PMID: 31811879 [PubMed – as supplied by publisher]

The Etiology, Diagnosis and Management of Hyperhidrosis: A Comprehensive Review. Part II. Therapeutic Options.

The Etiology, Diagnosis and Management of Hyperhidrosis: A Comprehensive Review. Part II. Therapeutic Options.

J Am Acad Dermatol. 2019 Jan 30;:

Authors: Nawrocki S, Cha J

Abstract
Hyperhidrosis (HH) is a chronic disorder of excess sweat production that may have a significant adverse effect on quality of life. A variety of treatment modalities currently exist to manage HH. Initial treatment includes lifestyle and behavioral recommendations. Antiperspirants are regarded as the first-line therapy for primary focal HH and can provide significant benefit. Iontophoresis is considered to be the primary remedy for palmar and plantar HH. Botulinum toxin (BTX) injections are administered at the dermal-subcutaneous junction and serve as a safe and effective treatment option for focal HH. Oral systemic agents are reserved for treatment-resistant cases or for generalized HH. Energy delivering devices such as lasers, ultrasound technology, microwave thermolysis, and fractional microneedle radiofrequency may also be utilized to reduce focal sweating. Surgery may be considered when more conservative treatments have failed. Local surgical techniques, particularly for axillary HH, include excision, curettage, liposuction, or a combination of these techniques. Sympathectomy is the treatment of last resort when conservative treatments are unsuccessful or intolerable, and after accepting secondary compensatory HH as a potential complication. A review of treatment modalities for HH and a sequenced approach are presented.

PMID: 30710603 [PubMed – as supplied by publisher]

The Etiology, Diagnosis and Management of Hyperhidrosis: A Comprehensive Review. Part I. Etiology and Clinical Work-Up.

The Etiology, Diagnosis and Management of Hyperhidrosis: A Comprehensive Review. Part I. Etiology and Clinical Work-Up.

J Am Acad Dermatol. 2019 Jan 30;:

Authors: Nawrocki S, Cha J

Abstract
Hyperhidrosis (HH) is a dermatologic disorder defined by sweat production beyond the thermoregulatory requirements. Clinically, HH is diagnosed when excess sweating creates significant emotional, physical, or social discomfort, causing negative impact on the patient’s quality of life. Existing data imply that this condition may affect at least 4.8% of the US population. The etiology of HH may stem from autonomic nervous system complex dysfunction, resulting in neurogenic overactivity of otherwise normal eccrine sweat glands. Alternatively, HH may be a result of aberrant central control of emotions. This condition is categorized as primary or secondary HH. Approximately 93% of patients with HH have primary HH, of whom >90% have a typical focal and bilateral distribution affecting the axillae, palms, soles, and craniofacial areas. Secondary HH presents in a more generalized and asymmetric distribution and is generated by various underlying diseases or medications. Secondary causes of HH need to be excluded prior to diagnosing primary HH.

PMID: 30710604 [PubMed – as supplied by publisher]

Hyperhidrosis: Management Options.

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Hyperhidrosis: Management Options.

Am Fam Physician. 2018 Jun 01;97(11):729-734

Authors: McConaghy JR, Fosselman D

Abstract
Hyperhidrosis is excessive sweating that affects patients’ quality of life, resulting in social and work impairment and emotional distress. Primary hyperhidrosis is bilaterally symmetric, focal, excessive sweating of the axillae, palms, soles, or craniofacial region not caused by other underlying conditions. Secondary hyperhidrosis may be focal or generalized, and is caused by an underlying medical condition or medication use. The Hyperhidrosis Disease Severity Scale is a validated survey used to grade the tolerability of sweating and its impact on quality of life. The score can be used to guide treatment. Topical aluminum chloride solution is the initial treatment in most cases of primary focal hyperhidrosis. Topical glycopyrrolate is first-line treatment for craniofacial sweating. Botulinum toxin injection (onabotulinumtoxinA) is considered first- or second-line treatment for axillary, palmar, plantar, or craniofacial hyperhidrosis. Iontophoresis should be considered for treating hyperhidrosis of the palms and soles. Oral anticholinergics are useful adjuncts in severe cases of hyperhidrosis when other treatments fail. Local microwave therapy is a newer treatment option for axillary hyperhidrosis. Local surgery and endoscopic thoracic sympathectomy should be considered in severe cases of hyperhidrosis that have not responded to topical or medical therapies.

PMID: 30215934 [PubMed – in process]

Postmenopausal craniofacial hyperhidrosis.

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Postmenopausal craniofacial hyperhidrosis.

Clin Exp Dermatol. 2018 Mar;43(2):180-182

Authors: Eustace K, Wilson NJ

Abstract
Hyperhidrosis is a condition marked by excessive sweating, which can either be localized or generalized. Primary focal hyperhidrosis (PFH) can arise from the palms, plantar feet, axillae and also from the face and scalp. PFH primarily affects a younger population of children and young adults, with the majority presenting before the age of 25 years. We report a distinct subtype of craniofacial hyperhidrosis in 20 postmenopausal women; this subtype is often under-recognized.

PMID: 29238998 [PubMed – indexed for MEDLINE]