# Presentation: 337902

## Recycling Psychiatric Medications for Smoking Cessation

**John Hughes, M.D.**
**University of Vermont**
**john.hughes@uvm.edu**

## Slide 2

## Rationales for Use of Psychiatric Medications forSmoking Cessation

**Substitution of beneficial effect**
**Self-medication**
**Anti-craving**
**Combat withdrawal**

## References

**Hughes JR, Stead LF, Lancaster T.  Anxiolytics for smoking cessation.  **_**The**_** **_**Cochrane Library**_**, Issue 4, 2000 Oxford**
**Hughes JR, Stead LF, Lancaster T.  **
**Antidepressants for smoking cessation, 2003 update.  **_**The Cochrane Library,**_** in press**

## Outcomes of Clinical Trials

- Antidepressants			Some effective
- Antipsychotics			Not tested
- Anticonvulsants			Not tested
- Anxiolytics				Some effective
- BZD blocker			Not tested
- Dopaminergic			Not well-tested
- Lithium				Not tested
- Opioid agonset			Not tested
- Opioid blocker			Not well-tested
- Sedatives				Not helpful
- Serotonin antagonists		Not tested
- Stimulants				Not well-tested
- THC blocker			Not tested

##  Antidepressant Treatmentsand Neurochemical Actions

- 		**Dopaminergic****	****Adrenergic****	****Serotonergic**
_**Effective**_
**Bupropion (20)       +  +  + ****	****	****     + + +****	****        --**
**Nortriptyline (5)          + +****	****	****     + + +****	****        --**
_**Not clear**_
**MAOIs (4)****	****               +****	****	****        + +****	****        --**
**Doxepin (1)****	****            + +****	****	****        + +****	****        +**
_**Not effective**_
**SSRIs (6)****	****	****   --****	****	****         --****	****	****      + + +**
**Imipramine (1)****	****   +****	****	****      + + +****	****        +**
**Venlafaxine (2)****	****+ +****	****	****         + +****	****        --**

## Percent abstinent at 1 Month in Buspirone Trial(Cinciripini, 95)

**	****	****	****Placebo****	****	****Buspirone**
**Low anxiety****	****      89%****	****	****	****60%**
**High anxiety****	****      61%****	****	****	****88%**

## Relapse Off Drugin Buspirone Study

**Relapse Off Drug****in Buspirone Study**

**Placebo**

**On**
**Drug**

**Off**
**Drug**

**Buspirone**

## Possible Mechanisms of Action

**Decrease craving**
**Decrease withdrawal**
**Decrease stimulus control**
**Decrease abstinence to lapse**
**Decrease lapse to relapse**
**Drug less efficacious via tolerance or blockade**
**Drug more aversive **

## Possible Proxy Variables

_**Nonhumans**_
**Increased/decreases rate of self-administration,**
**   ****breaking point, unit price**
**Reduces reinstatement**
**Reduces ability of cues to maintain responding**
**Blocks nicotine effects on ICSS**
**Withdrawal reduction**
**Substitutability as DS**
**Blocks nicotine DS**

## Extinction Models for Screening

_**Non Humans**_
**Increases sensitivity to punishment**
**   ****induced or alternate reinforcer-induced**
**   ****extinction**
**Decreases extinction responding **
**Decreases post-extinction reinstatement**

## Types of Extinction

**Remove lever****	****=****	****	****Hospitalization**
**Nonresponsive lever  = ****	****Nicotine free cigarettes**
**Punish responding  = ****	****Tobacco policy**
**Competing reinforcer =****	****Psychosocial treatment**

## Possible Proxy Variables

_**Humans**_
**Increased/decreased tobacco use**
**Break point in PR**
**Shift in unit price**
**Block drug-induced craving**
**Block stimuli's-induced craving**
**Craving suppression**
**Withdrawal**
**Short term abstinence**

## Possible New Models for Screening in Humans

**Decreasing monetary payments for**
**   ****abstinence**
**Decreased ability of stimuli to prompt **
**   ****drug use**
**Self-reported ease of abstinence**

## “Proof of Concept” Trials

**Pilot studies on best dose**
**Titrate to tolerable dose**
**Pick sample most likely to respond based**
**  ****on prior quit experience**
**Short term abstinence (e.g., 2 wks)**
**Exit interviews to determine mechanism**
**  ****of action**

## Final Words

**Important to distinguish between well tested**
**      ****negative results and not well tested results**
**Smokers tolerance for adverse events is very**
**      ****low**
**Use optional conditions for first tests; especially**
**      ****subjects, compliance, dose, duration of tx**