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

Inclusion Criteria:

1. Treatment refractory obsessive-compulsive disorder:

2. Aged 18~65 when signing informed consent, outpatient or inpatient, male orfemale.

3. Fits DSM-5 obsessive-compulsive disorder criteria.

4. Fits treatment refractory obsessive-compulsive disorder criteria (both i andii): i.Treated with at least 3 kinds of serotonin reuptake inhibitors (SSRIs) with atleast 2 kinds of 2nd generation antipsychotic medication as enhancement, enoughdosage 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 ofCognitive Behavior Therapy (CBT) or CBT-intolerant. d)Y-BOCS score ≥ 25 in screening period and baseline. e)CGI-S score ≥ 4 in screeningperiod and baseline. f)Patient and guardian agree to DBS implant and sign informedconsent after fully understood research aims, contents, anticipated treatments andrisks.

5. Treatment refractory schizophrenia:

6. Aged 18~65 when signing informed consent, outpatient or inpatient, male orfemale.

7. Fits DSM-5 schizophrenia criteria.

8. Course of disorder ≥ 5 years.

9. Fits treatment refractory schizophrenia criteria, one of the conditions below: i.Treated with more than 2 different anti-psychotic medications (clozapineexcluded), enough dosage (equivalent dosage as chlorpromazine ≥ 600mg/day), enoughcourse of treatment (≥ 12 weeks), no effect or intolerant. ii.Treated with enough dosage of clozapine (≥ 300mg/day or blood medicationconcentration ≥ 350ng/ml, enough course of treatment (≥ 12 weeks), no effect orintolerant. e)PANSS score ≥ 70 in screening period and baseline, and at least 1 item from 5items (P1, P2, P3, P5, P6) of PANSS positive symptom scale ≥ 4; or at least 3 itemsfrom 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 andbaseline. h)Patient and guardian agree to DBS implant and sign informed consentafter fully understood research aims, contents, anticipated treatments and risks.

10. Treatment refractory bipolar with depression:

11. Aged 18~65 when signing informed consent, outpatient or inpatient, male orfemale.

12. Fits DSM-5 bipolar I or bipolar II criteria, currently with depression episode.

13. Course of disorder ≥ 2 years.

14. Fits treatment refractory bipolar with depression criteria (treated with twodifferent kinds of treatment below, enough dosage and enough course oftreatment ≥ 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 ofmedication 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 orfailed (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 inscreening 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 fullyunderstood research aims, contents, anticipated treatments and risks.

15. Treatment refractory anorexia nervosa:

16. Aged 18~65 when signing informed consent, outpatient or inpatient, male orfemale.

17. Fits DSM-5 anorexia nervosa criteria, consider both restricting type andbinge-eating/purging type.

18. 10 ≤ BMI < 16 in screening period and baseline.

19. 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 ≥ 3times repeated inpatient history and bad treatment effect (can't complete treatmentor 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 toreinforced treatment, last for more than 1 year, with more than 2 times ofinvoluntary food intake. e)Patient and guardian agree to DBS implant and sign informed consent after fullyunderstood research aims, contents, anticipated treatments and risks.

20. Gambling disorder:

21. Aged 18~65 when signing informed consent, outpatient or inpatient, male orfemale.

22. Course of disorder ≥ 2 years.

23. Diagnosed as gambling disorder based on DSM-5, fits medium or severe diagnosticstandard (≥ 6 terms)

24. Received systemic treatment (such as medication and social mental intervention)but still has iterative thoughts of impulse or gambling behaviors.

25. Patient and guardian agree to DBS implant and sign informed consent after fullyunderstood research aims, contents, anticipated treatments and risks.

26. Adult autism:

27. Aged 18~65 when signing informed consent, outpatient or inpatient, male orfemale.

28. Fits DSM-5 autism spectrum disorder diagnostic standard, and there's severe,life-threatening iterative behaviors, and independently evaluated by twopsychiatric doctors.

29. AuBC score ≥ 62 in screening period and baseline.

30. CGI-S score ≥ 4 in screening period and baseline.

31. Course of disorder ≥ 10 years, received systemic behavior intervention ortraining ( such as critical reaction training, cognitive behavior intervention,language expression training, demonstration method, natural environmenttraining, patriarch training, social skill training, intervention based onstory tales, etc. ) but failed, or intolerant.

32. Patient and guardian agree to DBS implant and sign informed consent after fullyunderstood research aims, contents, anticipated treatments and risks.

Exclusion Criteria:

1. With mental disorders including physical mental disorders, paranoid personalitydisorder, delayed mental development etc.

2. Through clinical evaluation by investigators, there exists significant suicidebehavior risk.

3. From screening period to baseline, patients who has significant improvement inevaluation scores:

4. Obsessive compulsive disorder: Y-BOCS score decreased (or improved) ≥ 20%

5. Schizophrenia: PANSS score decreased (or improved) ≥ 20%

6. Bipolar with depression: MADRS score decreased (or improved) ≥ 20%

7. Anorexia nervosa: BMI improved ≥ 20%

8. Gambling: through evaluation by investigators, online gambling behavior issignificantly improved

9. Adult autism: AuBC score decreased (or improved) ≥ 20%.

10. With severe or unstable cardiovascular, inspiratory, liver, kidney, blood,endocrine, neural system or other system disorders.

11. Has neural system disorders including physical brain disorders, brain trauma,treatment-refractory seizure etc.

12. During screening period or baseline, abnormalities in patient's physicalexamination, laboratory examination, electrocardiogram examination, imagingexamination have significant clinical meaning, and patients who are considered unfitby investigators.

13. Implanted artificial cochlea, pacemaker, similar single-side or double-side productsor experienced other physical surgeries within half a year that are considered tohave effect on this trial by investigators.

14. DBS implant surgery taboos present and is considered unfit by investigators.

15. Diagnosed as HIV positive.

16. Female in gestation, lactation, or blood HCG / urine gestation test positive. Orpatients who can't take effective contraception actions during the trial. Orpatients planning to birth or give birth after the trial begins for 3 months.

17. Currently involved or involved in other medication or medical device clinical trials 3 months before the screening period.

18. Other patients who are considered unfit by investigators.