<p> Table 1. SSRIs: double-blind, placebo-controlled studies in pathological gambling</p><p>Citation Study Sample features Tx group Control Trial Outcomes Conclusions Design Group Length & Sponsor Blanco et al RA;DB; 32 pathological Fluvoxami Placebo 6 No significant differences Small sample study 2002 PC;N- gamblers, ne (FLV) up N=17 month in the proportion of showing no statistically ITT 13 completers at 6 to 200 1 drop-out s responders between significantly difference of months mg/day due to side- patients treated with FLV FLV from PL except in N=15 effects and those assigned to Pl males and younger 3 drop-outs for the overall trial patients due to side- effects Hollander et al RA;DB; 15 pathological Fluvoxami Placebo 8 75% of the pts were Small sample, crossover 2000 PC;N- gamblers, ne (FLV) up weeks judged treatment study showing the ITT 10 completers to 250 (12 responders (PG-CGI) to FLV effectiveness of FLV in PG. mg/day, weeks I phase I and 67% in phase Post hoc analysis, treating final mean ) II, as compared with 67% each phase as a separate dose 195 + responders to Pl in phase I trial, demonstrated a 50 mg/day and 25% in phase II significant difference N=15 between FLV and Pl in the 3 drop-outs 2nd phase of the trial but due to side- not in the 1st phase effects Kim et al 2002 RA;DB; 45 pathological Paroxetine Placebo 8 At the endpoint, the mean Small sample study PC;ITT gamblers, (PAR) up to N=22 weeks G-SAS total had decreased showing the superiority of 41 completers 60 mg/day 1 drop-out by 52% in the PAR group PAR over Pl in treating N=23 due to side- compared with 23% in the acute PG 1 drop-out effects Pl group. CGI-rates showed due to side- more than 60% of effects responders in the PAR group compared to less than 25% in the Pl group Grant et al RA;DB; 76 pathological Paroxetine Placebo 16 Treatment with PAR did Multicenter trial showing 2000 PC;ITT gamblers, (PAR) up to N=40 weeks not yield significantly no evidence of statistically 45 completers 60 mg/day 1 drop-out greater efficacy than significant advantage for N=36 due to side- placebo at study endpoint paroxetine on any of the 6 drop-outs effects as assessed by the PG-CGI outcomes measures due to side- effects RA= random assignment; DB= double-blind; SB= single-blind; UB= unblinded; PC= placebo controlled; UC= uncontrolled; ITT= intent-to-treat analysis</p><p>N-ITT= no intent-to-treat analysis</p><p>Table 2. SSRIs: single-blind, placebo-controlled and open-label studies in pathological gambling</p><p>Citation Study Sample features Tx group Control Trial Outcomes Conclusions Design Group Length Hollander et al NRA;SB 16 pathological Fluvoxami Placebo 16 At endpoint 7/10 patients Small sample study 1998 ;PC;N- gamblers, ne (FLV) up (Before weeks were judged responders showing the effectiveness ITT 10 completers, no to 300 receiving (much or very much of FLV in treating acute drop-out due to mg/day FLV, improved on CGI and pathological gambling side-effects Mean dose patients decrease < 25% on PG-Y- 220 mg/day entered an BOCS) 8-week lead in phase) Zimmerman NRA;UB 15 pathological Citalopram 12 13/15 10 patients were Small open-label trial et al 2002 ; gamblers, (CIT) up to weeks judged responders (much showing the efficacy of CIT UC;N- 8 of these with 60 mg/day or very much improved on in treating acute ITT major depression, Mean final CGI; PG-Y-BOCS 79.5%) pathological gambling 9 completers, dose 34.7 1 drop-out due to mg/day side-effects</p><p>RA= random assignment; DB= double-blind; SB= single-blind; UB= unblinded; PC= placebo controlled; UC= uncontrolled; N-ITT= no intent-to-treat analysis</p><p>Table 3. Other antidepressants (non SSRIs): open-label studies in pathological gambling</p><p>Citation Study Sample features Tx group Control Trial Outcomes Conclusions Design Group Length Pallanti et al NRA;UB 14 pathological, Nefazodon 8 9/12 completers were Small open-label study 2002 ; gamblers e (NEF) up weeks rated as responders on the showing the effectiveness UC;N- 12 completers, to 500 basis of both PG-CGI score of NEF in treating acute ITT no drop-out due to mg/day of 1 or 2 and a 25% pathological gambling side-effects Mean dose reduction in PG-Y-BOCS 345.8 score mg/day</p><p>Black et al NRA;UB 10 pathological Bupropion 8 7/10 patients were rated Small open-label study 2004 ; gamblers (BUP) up to weeks as responders on the basis showing the effectiveness UC;N- 300 mg/day of a PG-CGI score of 1 or 2 of BUP in treating acute ITT pathological gambling</p><p>RA= random assignment; DB= double-blind; SB= single-blind; UB= unblinded; PC= placebo controlled; UC= uncontrolled; N-ITT= no intent-to-treat analysis</p><p>Table 4. Opioid antagonists: double-blind, placebo-controlled and open-label studies in pathological gambling</p><p>Citation Study Sample features Tx group Control Trial Outcomes Conclusions Design Group Length Kim et al 2001 RA;DB; 45 pathological Naltrexone Placebo 12 At endpoint NLT showed The only DB, PC study PC;ITT gamblers, (NLT) N=20, N=25 weeks significant improvement with NLT showed the 36 completers, up to 250 over the placebo group in effectiveness of this opioid 4 pts developed mg/day all measures including PG- antagonist in treating elevated liver Mean dose CGI pathological gambling. transaminases 187 mg/day Besides those pts excluded during the enrollment, 4 other subjects developed elevated liver transaminases during the study period Grant et al NRA;UB 17 pathological Naltrexone 6 At endpoint, most patients Small open-label trial 2001 ; gamblers, (NLT) up to weeks had stopped their showing the efficacy of NLT UC;NITT 14 completers, 250 mg/day gambling behavior and in treating acute 2 drop-outs due to Mean final reported significant pathological gambling side-effects dose 157 decreases in the CGI and mg/day other gambling symptoms RA= random assignment; DB= double-blind; SB= single-blind; UB= unblinded; PC= placebo controlled; UC= uncontrolled; ITT= intent-to-treat analysis</p><p>N-ITT= no intent-to-treat analysis</p><p>Table 5. Mood stabilizers: randomized, placebo-controlled and active-comparison studies in pathological gambling</p><p>Citation Study Sample features Tx group Control Trial Outcomes Conclusions Design Group Length Hollander et al RA;DB; 40 pathological Lithium (LI) Placebo 10 Gambling severity was Small double-blind study 2005 PC;ITT gamblers with up to 1200 N=22 weeks statistically significantly the efficacy of lithium in comorbid bipolar II, mg/day, lower in the LI group than treating pathological bipolar NOS or Mean final in the Pl group at endpoint gamblers with bipolar cyclothymia), dose 1150 + based on the PG-YBOCS spectrum comorbidity 29 completers (12 215 mg/day and PG-CGI scores. LI compl, no drop- N=18 Significant improvements out due to side- in mood instability scores effects and 17 Pl on the CARS-M were also compl, no drop-out noted in the LI group vs due to side-effects) the Pl group Pallanti et al RA;SB; 42 pathological Lithium (LI) Valproate 14 At the endpoint both Small single-blind study 2002 AC;ITT gamblers, up to 1200 (VAL) up to weeks groups both groups showing that both mood- 31 completers (15 mg/day; 1500 showed significant mean stabilizers (LI and VAL) LI compl, 2 drop- N=23 mg/day percentage improvement were effective in the outs due to side- Mean final N=19 on PG-YBOCS score, but treatment of pathological effects and 16 VAL dose 795 + Mean final the improvement gambling compl, 1 drop-out 261 mg/day dose 830 + difference between groups due to side-effects) 280 was not statistically mg/day significant Dannon et al RA;AC; 31 pathological Topiramate Fluvoxami 12 At the endpoint both Small blind-rater 2005 NITT; gamblers, (TOP) up to ne (FLV) up weeks groups both groups comparison study showing Blind 20 completers (12 200 mg/day; to 200 showed significant mean that the mood-stabilizers raters TOP compl, 2 drop- N=15 mg/day percentage improvement TOP and the SSRI FLV outs due to side- N=16 on PG-CGI score, but the were equally effective in effects and 8 FLV improvement difference the treatment of compl, 5 drop-outs between groups was not pathological gambling due to side-effects) statistically significant</p><p>RA= random assignment; DB= double-blind; SB= single-blind; UB= unblinded; PC= placebo controlled; AC= active-comparison; UC= uncontrolled; ITT= intent-to-treat analysis</p>