Table 3. Randomized double-blinded placebo-controlled studies of nicotinic medications measuring cognition in schizophrenia.
| Experimental Medication |
Target Dose (mg/day) |
Dura- tion (Weeks) |
Design | Smokers | Antipsychotics | Randomized/ Completers |
Cognitive Battery | Results Compared to Placebo |
|
|---|---|---|---|---|---|---|---|---|---|
| Friedman 2002 |
Donepezil | 5 and 10 | 12 | Parallel | 78% | risperidone | 36/34 | CPT, DS, RAVLT, SSWMT, TMTA and B, VF, WCST |
placebo = donepezil 10 = donepezil 5 |
| Nahas 2003 | Donepezil | 10 | 12 each | Cross- over |
NA | olanzapine or risperidone |
6/6 | COWAT | placebo = donepezil |
| Tuğa 2004 | Donepezil | 5 | 6 each | Cross- over |
NA | fluphenazine or pimozide |
12/12 | TMTA and B, VF, WAIS (BD), WCST, WMS-R (DS, FG, LM, VePA, ViPA, ViR) |
placebo = donepezil |
| Freudenreich 2005 |
Donepezil | 10 | 8 | Parallel | 80% | Mostly olanzap- ine or risperi- done |
36/32 | BOWA, GP, HVLT, TMTA and B, WMS-R (DS) |
placebo = donepezil |
| Erickson 2005 |
Donepezil | 5 | 8 each | Cross- over |
NA | 1st or 2nd genera- tion |
24/15 | RAVLT, TMTA and B | RAVLT: donepezil > placebo |
| Mazeh 2006 | Donepezil | 10 | 12 | Parallel | NA | 1st or 2nd genera- tion |
20/17 | ADAS-cog | placebo = donepezil |
| Lee 2007 | Donepezil | 5 | 12 | Parallel | 58% | haloperidol | 24/23 | BNT, DS, DSST, HVLT, MMSE, RVLT, ST, TMTA and B, VF |
HVLT: donepezil > placebo MMSE, RVLT, DS: (trend) donepezil > placebo |
| Fagerlund 2007 |
Donepezil | 10 | 16 | Parallel | 64% | ziprasidone | 21/11 | BSRT, CANTAB (IED, SOC, SSP), DS, RCFT, TMTB, VF |
BSRT: placebo > donepezil SOC: (trend) placebo > donepezil |
| Kohler 2007 | Donepezil | 10 | 16 | Parallel | 46% | 2nd generation (no clozapine) |
26/22 | BDAE (AN, Reading), CPT,CVLT, DS, DSST, FT, JOLO, LNNB, MEA (Token Task, COWAT, VNT), SR, WAIS (BD), WCST, WMS-R (LM, VR) |
placebo = donepezil |
| Keefe 2008 | Donepezil | 10 | 12 | Parallel | 59% | 2nd generation (no clozapine) |
245/195 | CATIE Battery: CI, COWAT, CPT, GP, HVLT, LNTAWM, VWMT, WISC-III Mazes, WCST, WAIS (DSST) |
CI, COWAT: pla- cebo > donepezil |
| Akhindzadeh 2008 |
Donepezil | 10 | 12 | Parallel | NA | Risperidone | 30/30 | WAIS (BD), WCST, WMS-R (DS, FG, LM, VePA, ViPA, ViR) |
placebo = donepezil |
| Sharma 2006 | Rivastigmine | 12 | 24 | Parallel | 81% | Olanzapine, quetiapine, or risperidone |
40/21 | CPT, CVLT, DTS, FT, TMTA and B, VF, WCST, WAIS (DS, LNS) |
placebo = rivastig- mine |
| Kumari 2006 | Rivastigmine | 12 | 12 | Parallel | 81% | Olanzapine, quetiapine, or risperidone |
36/21 | n-back | placebo = rivastig- mine |
| Chouinard 2007 |
Rivastigmine | 9 | 24 | Parallel | 70% | 1st or 2nd genera- tion |
24/20 | CANTAB (PAL, RTI, RVIP, SOC, SWM) |
placebo = rivastigmine |
| Schubert 2006 |
Galantamine | 24 | 8 | Parallel | 94% | risperidone | 17/14 | CPT, OMMT, RBANS, TOT, UOA |
RBANS (Total score, attention and delayed memory items): galan- tamine > placebo |
| Lee 2007a | Galantamine | 16 | 12 | Parallel | NA | 1st generation | 24/22 | BNT, DS, DSST, HVLT, MMSE, RCFT, ST, TMTA, VF |
RCFT: donepezil > pla- cebo |
| Caroff 2007 | Galantamine | 8-24 | 12 each | Cross- over |
NA | 1st and 2nd generation |
38/35 | MMSE | placebo = galantamine |
| Dyer 2008 | Galantamine | 32 | 8 | Parallel | 0% | 2nd generation | 20/18 | CPT,GP, ST, WAIS (LNS) |
CPT, ST, LNS: placebo > galantamine |
| Sacco 2008 | Galantamine | 4 and 8 | 3 days | Cross- over |
57% | NA | 21/21 | CPT, DS, ST, TMTB, VSWM |
placebo = galantamine |
| Buchanan 2008 |
Galantamine | 24 | 12 | Parallel | 42% | 2nd generation (no clozapine), low dose 1st generation |
86/73 | BACS-NS, BVSMT, CPT, CVLT, GP, WAIS (DSST, LNS) |
DSST: galantamine > placebo CVLT: (trend) galan- tamine > placebo CPT: placebo > galan- tamine |
| Lindenmayer 2011 |
Galantamine | 24 | 24 | Parallel | NA | long acting injectable risperidone |
38/32 | CPT, FT, OWMT, PEAT, SST, STDT, WLMT |
placebo = galantamine |
| Hong 2011 | Varenicline | 2 | 8 | Parallel | 68% | 1st and 2nd generation |
69/59 | CPT, MCCB, WAIS (DSST) |
placebo = varenicline |
| Shim 2012 | Varenicline | 2 | 8 | Parallel | 52% | 1st and 2nd generation |
120/91 | CPT, DS, ST, VST, WAIS (DSST), WCST |
placebo = varenicline (smoking status had significant effects) |
| Velligan 2012 |
AZD3480 | 5, | 12 | Parallel | 100% | Olanzapine, quetiapine, or risperidone |
440/308 | IntegNeuro, WAIS(SS), BACS- SC |
placebo = AZD3480 |
| Olincy 2006 | DMXB-A | 150/75 or 75/37.5 |
3 days | Cross- over |
0% | 1st and 2nd generation |
13/12 | RBANS | Total Score: 75/37.5 > placebo |
| Freedman 2008 |
DMXB-A | 300 or 150 |
4 | Cross- over |
0% | 1st and 2nd generation |
31/31 | MCCB | Attention/Vigilance: 300 and 150 > placebo Working Memory: 300 > placebo, (trend) 150 > placebo Verbal Learning: placebo > 300 and 150 |
| Shiina 2010 | Tropisetror | 10 | 8 | Parallel | 28% | risperidone | 40/33 | CANTAB (DMS, IED, PRM, RVIP, SOC, SRM, SSP, SWM) |
RVIP (non-smokers): tropisetror > placebo |
| Lieberman 2013 |
TC-5619 | 25 | 12 | Parallel | 46% | quetiapine or risperidone |
185/154 | CSB, DSST, TMTA and B |
1-back, GMLT, SCI-Cog: (trend) TC-5619 > pla- cebo 1-back, GMLT (smok- ers): TC-5619 > placebo |
ADAS-Cog: Alzheimer Disease Assessment Scale – Cognitive subscale, AN: Animal naming, BACS-NS: Brief Assessment of Cognition in Schizophrenia, BD: Block Design, BDAE: Boston Diagnostic Aphasia Exam, BNT: Boston Naming Task, BOWA: Benton Oral Word Association Test, BSRT: Buschke Selective Reminding Test, BVSMT: Brief Visuospatial Memory Test, CI: Category Instances, COWAT: Controlled Oral Word Association Test, CPT: Continuous Performance Test, CSB: CogState Schizophrenia Battery, CVLT: California Verbal Learning Task, DMS: Delayed Matching to Sample, DS: Digit Span, DSST: Digit Symbol Substitution Test, DTS: Dot Test Score, FG: Figural memory, FT: Finger Tapping, GMLT: Groton Maze Learning Task, GP: Grooved Pegboard, HVLT: Hopkins Verbal Learning Task, IED: Intra-Extra Dimensional Set Shifting, JOLO: Judgment of Line Orientation, LM: Logical Memory, LNNB: Luria-Nebraska Neuropsychological Battery (stereognosis), LNS: Letter Number Sequence, LNTAWM: Letter-Number Test of Auditory Working Memory, MAE: Multilingual Aphasia Exam, MCCB: MATRICS (Measurement and Treatment Research to Improve Cognition in Schizophrenia) Consensus Cognitive Battery, MMSE: Mini-Mental State Examination, NS: Number Sequencing, OMMT: Object Matching Memory Test, OWMT: Object Working Memory Test, PAL: Paired Associates Learning, PEAT: Penn Emotional Acuity Test, PRM: Pattern Recognition Memory, RAVLT: Rey Auditory Verbal Learning Test, RBANS: Repeatable Battery for the Assessment of Neuropsychological Status, RCFT: Rey Complex Figure Test, RTI: Reaction Time, RVIP: Rapid Visual Information Processing, RVLT: Rey Visual Learning Test, SC: Symbol Coding, SGI-Cog: Subject Global Impression-Cognition, SOC: Stocking of Cambridge, SR: Seashore Rhythm, SRM: Spatial Recognition Memory, SSP: Spatial Span, SST: Set Shifting Test, SSWMT: Simple Spatial Working Memory Test, ST: Stroop Test, STDT: Strategic Target Detection Test, SWM: Spatial Working Memory, TMTA and B: Trail Making Test Part A and B, TOT: Tower of Toronto, UOA: Unirhinal Olfactory Acuity Test, VePA: Verbal Paired Associates, VF: Verbal Fluency, ViPA: Visual Paired Associates, ViR: Visual Reproduction, VNT: Visual Naming Task, VST: Visual Span Test, VSWM: Visuospatial working memory, VWMT: Visuospatial Working Memory Test, WAIS: Weschler Adult Intelligence Scale, WCST: Wisconsin Card Sorting Test, WISC-III: Wechsler Intelligence Scale for Children-Third Edition, WLMT: Word List Memory Test, WMS-R: Weschler Memory Scale-Revised