The emerging use of technology for the treatment of depression and other neuropsychiatric disorders.

BACKGROUND: Our objective is to review emerging technologies intended for the treatment of depression and other neuropsychiatric disorders. METHODS: These technologies include repetitive transcranial magnetic stimulation (rTMS), magnetic seizure therapy (MST), vagus nerve stimulation (VNS), deep brain stimulation (DBS), cortical brain stimulation (CBS), and quantitative electroencephalography (QEEG). RESULTS: The rationale for these technologies, their mechanisms of action, and how they are used in clinical practice are described. rTMS and VNS are effective for treatment-resistant depression. DBS is effective for resistant obsessive-compulsive disorder. QEEG can help predict a patient's response to an antidepressant. All of these technologies continue to be investigated in treatment studies. CONCLUSIONS: As these and other emerging technologies for depression and other neuropsychiatric disorders are development and applied, psychiatrists should understand the rationale for these modalities, how they work, and how they can be used in clinical practice.

Exploratory randomized clinical study of pagoclone in persistent developmental stuttering: the EXamining Pagoclone for peRsistent dEvelopmental Stuttering Study.

INTRODUCTION: Stuttering is a speech disorder in which the flow of speech is disrupted by repetitions, prolongation, and blocks of sounds, syllables, or words. No pharmacological treatments are approved for use in stuttering, and the most common form of treatment is speech therapy. This study was designed to assess the safety, tolerability, and effectiveness of pagoclone during 8 weeks of double-blind treatment followed by a 1-year open-label extension in patients who stutter. METHODS: An 8-week, multicenter, parallel-group, 2-arm, randomized (ratio 2:1 pagoclone-placebo), double-blind study with a 1-year open-label extension conducted at 16 US centers, including men and women aged 18 to 65 years who developed stuttering before 8 years of age. Twice-daily dosing with pagoclone (n = 88 patients) or matching placebo (n = 44 patients), with primary and secondary efficacy variables defined a priori, including Stuttering Severity Instrument Version 3 outcomes, clinician global impressions of improvement, and the change in the percentage of syllables stuttered. RESULTS: Pagoclone produced an average 19.4% reduction in percentage of syllables stuttered compared with 5.1% reduction for placebo. During open-label treatment, a 40% reduction in the percent syllables stuttered was observed after 1 year of treatment with pagoclone. The most commonly reported adverse event during double-blind treatment was headache (12.5% pagoclone patients, 6.8% placebo patients). DISCUSSION: Pagoclone was effective in reducing symptoms of stuttering and was well tolerated. In light of its favorable tolerability profile, as well as consistency of effects across multiple efficacy variables, pagoclone may have potential as a pharmacological treatment of stuttering. LIMITATIONS: The main limitation of this study was the adequacy of the number of subjects who participated because this study was conducted as a pilot investigation. Furthermore, as this condition waxes and wanes, the assessment of stuttering within the clinic setting may not be an adequate reflection of the stuttering of the patients within the community.

Use of ECT in Major Vascular Neurocognitive Disorder with Treatment-Resistant Behavioral Disturbance following an Acute Stroke in a Young Patient.

The following case describes the utilization of bitemporal ECT as a treatment of last resort in a 47-year-old woman with profoundly treatment-resistant behavioral disturbance poststroke. The use of ECT led to improvement in symptoms sufficient for discharge from an inpatient psychiatric unit to the nursing home. Neuropsychiatric sequelae of stroke include poststroke depression, anxiety, mania, psychosis, apathy, pathological laughter and crying, catastrophic reaction, and mild and major vascular neurocognitive disorders. Behavioral disturbance is common and may pose diagnostic and therapeutic difficulty in the poststroke patient. In most cases, first-line treatment includes pharmacologic intervention tailored to the most likely underlying syndrome. Frequent use of sedating medications is a more drastic option when behaviors prove recalcitrant to first-line approaches and markedly affect quality of life and patient safety. ECT is generally safe, is well tolerated, and may be effective in improving symptoms in treatment-resistant behavioral disturbance secondary to stroke with major neurocognitive impairment, as suggested in this case.

A Randomized Sham-Controlled Trial of Deep Brain Stimulation of the Ventral Capsule/Ventral Striatum for Chronic Treatment-Resistant Depression.

BACKGROUND: Multiple open-label trials of deep brain stimulation (DBS) for treatment-resistant depression (TRD), including those targeting the ventral capsule/ventral striatum target, have shown encouraging response rates. However, no randomized controlled trials of DBS for TRD have been published. METHODS: Thirty patients with TRD participated in a sham-controlled trial of DBS at the ventral capsule/ventral striatum target for TRD. Patients were randomized to active versus sham DBS treatment in a blinded fashion for 16 weeks, followed by an open-label continuation phase. The primary outcome measure was response, defined as a 50% or greater improvement on the Montgomery-Åsberg Depression Rating Scale from baseline. RESULTS: There was no significant difference in response rates between the active (3 of 15 subjects; 20%) and control (2 of 14 subjects; 14.3%) treatment arms and no significant difference between change in Montgomery-Åsberg Depression Rating Scale scores as a continuous measure upon completion of the 16-week controlled phase of the trial. The response rates at 12, 18, and 24 months during the open-label continuation phase were 20%, 26.7%, and 23.3%, respectively. CONCLUSION: The results of this first randomized controlled study of DBS for the treatment of TRD did not demonstrate a significant difference in response rates between the active and control groups at the end of the 16-week controlled phase. However, a range of 20% to 26.7% of patients did achieve response at any time during the open-label continuation phase. Future studies, perhaps utilizing alternative study designs and stimulation parameters, are needed.

Pharmacotherapy of mood disorders.

The mood disorders-primarily major depressive disorder and bipolar affective disorder-constitute one of the world's greatest public health problems and are associated with significant reductions in productivity, health, and longevity. In addition, people who suffer from these common illnesses, along with their families and loved ones, experience an incalculable toll on quality of life. Dating to the introduction of the first effective therapies for mood disorders in the late 1950s and 1960s, various types of pharmacotherapy have become a mainstay for the management of mood disorders, particularly more severe, chronic, and recurrent forms of depression and most forms of bipolar disorder. This review examines recent developments in the pharmacotherapy of both forms of mood disorder, comparing the newer antidepressants such as the selective serotonin reuptake inhibitors and serotonin norepinephrine reuptake inhibitors with their predecessors (the monoamine oxidase inhibitors and tricyclic antidepressants) and likewise comparing the older standard for management of bipolar disorder, lithium, with newer classes of medications, such as a selected group of anticonvulsants and the atypical antipsychotics. Although these newer classes of medications have generally improved upon the earlier treatments in terms of better tolerability and safety, there are no universally effective pharmacologic treatments for mood disorders, and careful medical management of these medications is still warranted.