Efficacy and Safety of Combo-stim Deep Brain Stimulation for Treatment-refractory Mental Disorders

Prior treatment

• DBS implant surgery taboos present and is considered unfit by investigators.
• Currently involved or involved in other medication or medical device clinical trials 3 months before the screening period.

Other illness

• With mental disorders including physical mental disorders, paranoid personality disorder, delayed mental development etc.
• From screening period to baseline, patients who has significant improvement in evaluation scores:
  • Obsessive compulsive disorder: Y-BOCS score decreased (or improved) ≥ 20%
  • Schizophrenia: PANSS score decreased (or improved) ≥ 20%
  • Bipolar with depression: MADRS score decreased (or improved) ≥ 20%
  • Anorexia nervosa: BMI improved ≥ 20%
  • Gambling: through evaluation by investigators, online gambling behavior is significantly improved
  • Adult autism: AuBC score decreased (or improved) ≥ 20%.
• With severe or unstable cardiovascular, inspiratory, liver, kidney, blood, endocrine, neural system or other system disorders.
• Has neural system disorders including physical brain disorders, brain trauma, treatment-refractory seizure etc.
• Diagnosed as HIV positive.

Lab values

• During screening period or baseline, abnormalities in patient's physical examination, laboratory examination, electrocardiogram examination, imaging examination have significant clinical meaning, and patients who are considered unfit by investigators.

Other

• Through clinical evaluation by investigators, there exists significant suicide behavior risk.
• Implanted artificial cochlea, pacemaker, similar single-side or double-side products or experienced other physical surgeries within half a year that are considered to have effect on this trial by investigators.
• Female in gestation, lactation, or blood HCG / urine gestation test positive. Or patients who can't take effective contraception actions during the trial. Or patients planning to birth or give birth after the trial begins for 3 months.
• Other patients who are considered unfit by investigators.

• Treatment refractory obsessive-compulsive disorder:
  • Aged 18\~65 when signing informed consent, outpatient or inpatient, male or female.
  • Fits DSM-5 obsessive-compulsive disorder criteria.
  • Fits treatment refractory obsessive-compulsive disorder criteria (both i and ii):
  • i.Treated with at least 3 kinds of serotonin reuptake inhibitors (SSRIs) with at least 2 kinds of 2nd generation antipsychotic medication as enhancement, enough dosage and enough course of treatment, and still no effect or intolerant.
  • ii.While using enough dosage of SSRIs, treated with more than 8\~12 times of Cognitive Behavior Therapy (CBT) or CBT-intolerant.
  • d)Y-BOCS score ≥ 25 in screening period and baseline. e)CGI-S score ≥ 4 in screening period and baseline. f)Patient and guardian agree to DBS implant and sign informed consent after fully understood research aims, contents, anticipated treatments and risks.
• Treatment refractory schizophrenia:
  • Aged 18\~65 when signing informed consent, outpatient or inpatient, male or female.
  • Fits DSM-5 schizophrenia criteria.
  • Course of disorder ≥ 5 years.
  • Fits treatment refractory schizophrenia criteria, one of the conditions below:
  • i.Treated with more than 2 different anti-psychotic medications (clozapine excluded), enough dosage (equivalent dosage as chlorpromazine ≥ 600mg/day), enough course of treatment (≥ 12 weeks), no effect or intolerant.
  • ii.Treated with enough dosage of clozapine (≥ 300mg/day or blood medication concentration ≥ 350ng/ml, enough course of treatment (≥ 12 weeks), no effect or intolerant.
  • e)PANSS score ≥ 70 in screening period and baseline, and at least 1 item from 5 items (P1, P2, P3, P5, P6) of PANSS positive symptom scale ≥ 4; or at least 3 items from PANSS negative symptom scale (N1\~N7) ≥ 4, or at least 2 items ≥ 5.
  • f)CGI-S ≥ 4 in screening period and baseline. g)GAF ≤ 60 in screening period and baseline. h)Patient and guardian agree to DBS implant and sign informed consent after fully understood research aims, contents, anticipated treatments and risks.
• Treatment refractory bipolar with depression:
  • Aged 18\~65 when signing informed consent, outpatient or inpatient, male or female.
  • Fits DSM-5 bipolar I or bipolar II criteria, currently with depression episode.
  • Course of disorder ≥ 2 years.
  • Fits treatment refractory bipolar with depression criteria (treated with two different kinds of treatment below, enough dosage and enough course of treatment ≥ 8 weeks, and cannot acquire symptom cure for 8 consecutive weeks, either i or ii):
  • i.Used at least two medications (alone) among Olanzapine (10-20mg/d) + Fluoxetine (20-60mg/d), Quetiapine (200-600mg/d), Lurasidone (40-160mg/d), Lamotrigine (200-400mg/d) ii.Used at least one medication above (alone), and used one of medication above with another medication among Lamotrigine (200-400mg/d), Valproate (1000-2000mg/d) and lithium salt (blood lithium reaches 0.8mmol/L).
  • e)Upon medication treatment, electroconvulsive therapy ≥ 12 times, no effect or failed (such as intolerant).
  • f)Fits severe symptom criteria: i.Depression episode ≥ 12 weeks in screening period. ii.MADRS score ≥ 26 in screening period and baseline. iii.GCI-BP score ≥ 4 in screening period and baseline. iv.YMRS score ≥ 12 in screening period and baseline. g)Patient and guardian agree to DBS implant and sign informed consent after fully understood research aims, contents, anticipated treatments and risks.
• Treatment refractory anorexia nervosa:
  • Aged 18\~65 when signing informed consent, outpatient or inpatient, male or female.
  • Fits DSM-5 anorexia nervosa criteria, consider both restricting type and binge-eating/purging type.
  • 10 ≤ BMI \< 16 in screening period and baseline.
  • Fits treatment refractory anorexia nervosa criteria (both i, ii, iii and iv):
  • i.Course of disorder ≥ 5 years, severe and sustained anorexia nervosa. ii.With ≥ 3 times repeated inpatient history and bad treatment effect (can't complete treatment or immediate relapse after treatment).
  • iii.Through systemic nutrient treatment, medication (SSRIs and/or anti-psychotics), psychotherapies (such as reinforced CBT, FBT treatment), no effect or intolerant.
  • iv.Worsened instability of clinical treatment, refuse treatment or bad reaction to reinforced treatment, last for more than 1 year, with more than 2 times of involuntary food intake.
  • e)Patient and guardian agree to DBS implant and sign informed consent after fully understood research aims, contents, anticipated treatments and risks.
• Gambling disorder:
  • Aged 18\~65 when signing informed consent, outpatient or inpatient, male or female.
  • Course of disorder ≥ 2 years.
  • Diagnosed as gambling disorder based on DSM-5, fits medium or severe diagnostic standard (≥ 6 terms)
  • Received systemic treatment (such as medication and social mental intervention) but still has iterative thoughts of impulse or gambling behaviors.
  • Patient and guardian agree to DBS implant and sign informed consent after fully understood research aims, contents, anticipated treatments and risks.
• Adult autism:
  • Aged 18\~65 when signing informed consent, outpatient or inpatient, male or female.
  • Fits DSM-5 autism spectrum disorder diagnostic standard, and there's severe, life-threatening iterative behaviors, and independently evaluated by two psychiatric doctors.
  • AuBC score ≥ 62 in screening period and baseline.
  • CGI-S score ≥ 4 in screening period and baseline.
  • Course of disorder ≥ 10 years, received systemic behavior intervention or training ( such as critical reaction training, cognitive behavior intervention, language expression training, demonstration method, natural environment training, patriarch training, social skill training, intervention based on story tales, etc. ) but failed, or intolerant.
  • Patient and guardian agree to DBS implant and sign informed consent after fully understood research aims, contents, anticipated treatments and risks.