A pilot study of low-intensity focused ultrasound for treatment-resistant generalized anxiety disorder

Kennedy D. Mahdavi, Sheldon E. Jordan, Kaya G. Jordan, Elisabeth S. Rindner, Jonathan M. Haroon, Barshen Habelhah, Sergio A. Becerra, Jean Rama Surya, Victoria Venkatraman, Margaret A. Zielinski, Norman M. Spivak, Alexander Bystritsky, Taylor P. Kuhn

Journal of Psychiatric Research 2023 · 10.1016/j.jpsychires.2023.10.039

human patientanxietyclinical scale

Abstract

Objective This study intended to evaluate a possible therapeutic effect among patients with treatment-refractory generalized anxiety disorder (trGAD) by using transcranial focused ultrasound (tfUS) to modulate amygdalar activity. Methods Twenty-five participants with severe trGAD as outlined in the DSM-V were recruited from Los Angeles neurology and psychiatry clinics. All participants completed eight weekly 10-min tfUS sessions targeting the right amygdala. Functional and structural neuroimaging were used to navigate individual targets. Outcome measures including the Hamilton Anxiety Inventory (HAM-A, primary outcome) and Beck Anxiety Inventory (BAI) were collected at baseline and protocol completion. Upon study completion, participants were asked to report perceived change in clinical status using the Patient Global Impression - Improvement (PGI-I) scale. Data was collected from May 2020 through January 2023. Results All participants were able to tolerate treatment without notable side effects. No adverse events were reported. A Wilcoxon Signed-Rank Test was conducted to compare pre- and post-tfUS measures of anxiety. tfUS resulted in a significant decrease in anxiety as measured by the HAM-A (W = -3.69, p Conclusion This study provides preliminary evidence supporting the safety and efficacy of tfUS as a clinical intervention. These results warrant further investigation of tfUS as a therapeutic intervention for anxiety and other psychiatric and neurological disorders. Clinicaltrials Gov identifier NCT04250441.

Abstract via europepmc.

Specieshuman

Subjects25 participants

Sessions per subject8

Randomisedno

Blindingnone

Sham / controlnone

Auditory controlnot reported

Readout timingoffline

Anaesthesianot applicable

Readoutsclinical scale — HAM-A (primary); BAI; PGI-I

Direction of effectnot assessedNo neural activity was measured. Anxiety scores fell from baseline to completion (HAM-A pre-post change -12.64, BAI -12.88) in an open-label, uncontrolled design.

Adverse eventsnone observedAll participants tolerated treatment without notable side effects; no adverse events were reported.

Exposures

Exposure 1: right amygdala, 8 weekly sessions

Target: amygdala — “right amygdala”
Device: BrainSonix · Brainsonix · Brainsonix Pulsar 1002 ✓

Pulse timing
Waveform	pulsed
Fundamental frequency (kHz)	650	✓✓✓
Pulse duration (ms)	5	✓✓✓
Pulse repetition frequency (Hz)	10	✓✓✓
Duty cycle (%)	5pulse duration × PRF gives 5%	✓✓✓
Sonication duration (s)	30	✓✓✓

Pressure and intensity, by domain
Free-field pressure (kPa)	not reported
Free-field Isppa (W/cm²)	not reported
Free-field Ispta (W/cm²)	not reported
In-situ estimate	not reported
In-situ pressure (kPa)	not reported
In-situ Isppa (W/cm²)	14.39	✓✓✓
In-situ Ispta (W/cm²)	0.72	✓✓✓
Pressure, domain unspecified (kPa)	610	✓✓✓

Protocol, in the paper’s words

The tFUS was administered 30 s on and 30 s off for 10 min; eight consecutive weekly 10-min sessions.

Flags from extraction

exposures[0].unspecified_domain.isppa_w_cm2 — Reported as ISPPA.3 / ISPTA.3 (derated, subscript .3) but the paper does not say these are in situ values; kept in unspecified_domain.
exposures[0].unspecified_domain.ispta_w_cm2 — Paper gives 719.73 mW/cm2; converted to 0.71973 W/cm2.
n_sessions_per_subject — Sessions stated as eight weekly sessions; quote is the '8-week protocol' sentence.