Question

You are designing a small randomized trial (a pilot study) to compare ketamine (given by infusion) to placebo (also given by infusion) for treatment-resistant depression in adolescents ages 12 to 17 years. (Someone with treatment resistant depression has tried many anti-depressant therapies/medications which have not successfully alleviated the depression.) You are concerned that people you recruit to this study:

- may be at different stages of development (puberty, brain development, etc.) because of the age range;

- may have different histories of which anti-depressant treatments that they have tried but failed on;

- may have different co-morbidities (e.g., a concurrent diagnosis of anxiety)

Keeping in mind that this is a pilot study and the number of persons recruited will be small (thus the number of persons randomized to each treatment arm will be small), describe a randomization technique you would use to allocate people to ketamine vs. placebo.

Answer 1

Placebo is a medicine or procedure or treatment prescribed for the psychological benefits to the patient rather than for any physiological effect..
Ketamine is an antogonist at the N-methyl-d-asparate(NMDA) receptor.Produces rapid antidepressant affect with low,subaneasthetic doses of 0.5mg/kg by IV over 40min..clinical trial in medication free hospitalized patient with MDD demonstrated with single dose of sub-anesthesia dose of IV ketamine(0.5mg/kg over 40min)using indentical palcebo controlled,double-blind,cross-over designs..Results after several hours 50%patients met responces in 72hours following IV ketamine,some responded in 1week unexpalined by ketamine's short elimination half-life transient psychotomimetic side-effects normalized within 2hours of infusion in all patients..
Randamization:
    There are two-phase of studies
Phase 1, will be 2 weeks psychotropic medication washout period,24hours admission to the general clinic for randamized,double-blind pretreatment with a single dose of placebo,followed by open-lable Iv ketamine and assessment,24hours responders,48hours and 72hours post ketamine outpatient visits..patient those who are responding well will go for phase 2, a 32-d,randamized double-blind,flexible-dose..continuation trial of placebo..Need informed consent prior to the participation..initial vitals,weight checking,ECG.blood test and LFT,urine toxicology and hcg test will be performed..patient those who are long term ketamine,pcp or riluzole will be excluded for this trial..
    Patient who met the criteria for phase 1 allocated for placebo by a permuted block procedure..based on this list,the pharmacy distributed some general clinical research center(GCRC) 3 capsules(100mg placebo or lamotrigine)..a seperate randamization list allocated to riluzole or placebo for phase 2 participants..Next day morning patient came to clinic with fasting repeat urine test and procedure..following baseline ratings,2hours prior to IV ketamine infusion,patients received 300mg lamotrigine or placebo by mouth..this medicine level will be in peak by 1-4hours..Repeat ratings prior to ketamine infusion after 1hour,monitor ECG,administer oxygen,ketamine with noraml saline diluted infusion over 40min started for 2hours after palcebo ingestion..
    Mood rating were conducted at baseline pretreatment placebo at 40,120,180 and 240 min following IV infusion and at 24,48,72 hour post-ketamine and included Montgomery-Asberg Deression Rating scale(MADRS) and young mania rating scale.. raters individual will be graduated,well trained, nd experrience in MADRS and BPRS-positive symptoms subscale..
Conclusion:
   These pilot study show IV ketamine is well tolerated in TRD..and having rapid antideprassant properties..Lamotrigine or placebo pretreatment did not show acute efficacy of IV ketamine..provided relapse of depressive syptoms..to control investigation that maintain the initial response ,as well as active-control comparator trials of IV ketamine needed..