March 2005
Volume XI, Issue 1
West Virginia University Charleston Division
EDITOR-IN-CHIEF - Kristy Lucas, Pharm.D.
CO-EDITOR - Greg Rosencrance, M.D.
tients with ED. These include oral medica-
Phosphodiesterase type 5 (PDE5) Inhibitors
tions, vacuum constriction devices, psycho-
Justin M. Legge, Pharm.D. Candidate
logical sex therapy, penile self-injection ther-
apy, transurethral alprostadil, and penile pros-
theses. Many of the current options are inva-
sive and unappealing to patients. Due to sim-
Laura McKee, Pharm.D.
plicity, the most accepted form of ED treat-
ment is oral medication. The most effective
John Petts, Pharm.D.
oral treatments are the PDE5 inhibitors.
Among the PDE inhibitors, the question arises
as to which drug is regarded as the agent of
Erectile dysfunction (ED) is a very common sexual first choice. There are a number of similarities
dysfunction affecting approximately 52% of men between the agents, but notable differences
aged 40 to 70 years. All in all, ED affects as many also exist. Knowing the details and differ-
as 20 to 30 million men in the United States alone. ences between each drug can further provide
According to the National Institute of Health (NIH), a better strategy for agent selection. A num-
ED is defined as the persistent inability to achieve ber of contraindications and warnings exist for
and/or maintain an erection adequate to allow for all of the agents and can be of real concern if
satisfactory sexual intercourse. There are a vari- not emphasized. A difference exists between
ety of causes for ED and a number of treatment the drugs taken concurrently with alpha-
options, but the mainstays of ED therapy due to blockers. A low dose of sildenafil can be used
the simplicity of their use are the phosphodi- concurrently with an alpha-blocker, while con-
esterase type 5 (PDE5) inhibitors. This class of comitant use of vardenafil and tadalafil with an
drugs works by inhibiting the breakdown of PDE5 alpha-blocker is contraindicated. Pharmacoki-
thereby increasing cGMP levels leading to smooth netic differences also exist between the drugs.
muscle relaxation and increased penile blood flow, Sildenafil and vardenafil display a half-life of 3
which produces an erection. Viagra® (sildenafil) to 4 hours, while tadalafil has a half-life of 18
was the first PDE5 inhibitor approved for the treat- hours and has been shown to be effective up
ment of ED in March of 1998. Since then, to 36 hours after administration. Onsets of ac-
Levitra® (vardenafil) was approved in August of 2003 followed by Cialis® (tadalafil) in November of 2003 as the next PDE5 inhibitors approved for ♦PDE5 Inhibitors
Therapeutic Recommendation
Cymbalta® (duloxetine)
A variety of treatment options exist for pa-
A Primary Care Physician’s Guide to Newly Released Medications
to the maximum recommended dose of 100 mg or tion are very comparable among the three
agents along with slightly different adverse
effect profiles. Sildenafil is associated with a
Vardenafil is available as 2.5 mg, 5 mg, 10 mg, slightly greater incidence of visual distur-
and 20 mg tablets. The recommended starting bances, while tadalafil displays a greater
dose for most patients is 10 mg taken about 1 chance of back pain.
hour prior to sexual activity. The dose may be in-
According to clinical trials, sildenafil, varde-

creased to a maximum of 20 mg or decreased to 5 nafil, and tadalafil have all shown to be effec-
mg depending on efficacy and side effects. tive in the treatment of ED. Rates of success-
Tadalafil is available in 5 mg, 10 mg, and 20 mg ful penetration and successful intercourse im-
tablets. The starting dose of tadalafil is 10 mg to prove with the use of any of the PDE5 inhibi-
be taken one half hour to four hours prior to antici- tors as compared to placebo with each study
pated sexual activity. The dose may be increased resulting in p values of less than 0.05. Since
to a max of 20 mg or decreased to 5 mg based on efficacy appears to be comparable between all
of the drugs, other factors need to play in to
the decision as to which agent is started. At
In most instances, the maximum recommended this point, long-term data does not exist for
dosing frequency for any of these drugs is once vardenafil or tadalafil, while sildenafil displays
per day. Other risk factors may warrant lower more long-term data to support its use for the
starting doses for any of these agents (See Spe- treatment of ED. When choosing an agent, the
duration of effect with tadalafil may be a con-
sideration; however, sildenafil’s long term data

Cost Comparison
and other slight advantages make it a reason-
able first choice among the PDE5 inhibitors.

Dosing and Administration
Cialis® (tadalafil) 10 mg
Sildenafil is available in 25 mg, 50 mg, and 100 mg tablets. The recommended dose for most pa- Levitra® (vardenafil) 10mg
tients is 50 mg taken, as needed, approximately 1 Viagra® (celecoxib) 50 mg
hour before sexual activity. Based on effective- * Cost respresents the price of 6 tablets at average doses used.
ness and tolerability, the dose may be increased Contraindications

Administration of sildenafil, vardenafil, and tadala-
…A Primary Care
fil with any form of nitrates is contraindicated. All Physician’s Guide to
of the PDE5 inhibitors may further exacerbate the hypotensive effects of the nitrates. The co- Newly Released
administration of vardenafil or tadalafil with an al- Medications…
pha-blocker is contraindicated because of the ad-ditive hypotensive effects that the combination Departments of Internal Medicine
would produce. On the contrary, data supports and Clinical Pharmacy
the use of Flomax® (tamsulosin) 0.4mg qd with West Virginia University
tadalafil as safe. Any of these drugs should also Charleston Division
not be taken by patients with a known hypersensi- Warnings/Precautions
Sexual activity is associated with a potential for cardiac risk in patients with pre-existing cardiovas-cular disease. The use of PDE5 inhibitors for the Visit New Drug Update online at:
www.hsc.wvu.edu/charleston/sopc/nduhome.html treatment of ED is not recommended in these pa-tients because of their underlying conditions. A Primary Care Physician’s Guide to Newly Released Medications
Patients with left ventricular outflow obstructions impaired in patients with mild to moderate renal and those with severely impaired autonomic con- insufficiency. In patients with severe renal impair- trol of blood pressure can be particularly sensitive ment, however, the clearance of sildenafil was re- to the action of vasodilators, including PDE5 in- duced resulting in a reduced recommended start- ing dose of sildenafil of 25 mg. No dosage adjust- ment for tadalafil is necessary in patients with mild Patients who should not use any of the PDE5 in- renal impairment. Patients with moderate renal hibitors because of lack of safety and efficacy data insufficiency should start with 5 mg daily of tadala- include patients who have suffered a MI or stroke fil and not exceed 10 mg in a 48 hr period. Pa- within the last 6 months; unstable angina; uncon- tients with severe renal impairment or on hemodi- trolled arrhythmias; hypotension (<90/50) or un- alysis should only take a maximum recommended controlled hypertension; severe cardiac failure or CAD; and patients with a known hereditary degen- erative disorder such as retinitis pigmentosa. Hepatic Impairment: For vardenafil, no dosage adjustment is needed for patients with mild he- An erection lasting greater than 4 hours and priap- patic impairment (Child-Pugh A). The recom- ism (painful erections greater than 6 hours in du- mended starting dose in patients with moderate ration) have been reported in some instances for hepatic impairment (Child-Pugh B), however, is patients taking PDE5 inhibitors. If an erection 5mg of vardenafil because of decreased clear- lasts longer than 4 hours, patients should seek ance of the drug. The maximum recommended immediate medical assistance to help prevent per- dose is not to exceed 10mg. Vardenafil was not studied in patients with severe hepatic impairment Although the concurrent use of alpha-blockers (Child-Pugh C). A starting dose of 25 mg of silde- with vardenafil or tadalafil is contraindicated, the nafil is recommended for patients with any level of combination of an alpha-blocker with sildenafil is hepatic impairment. Patients with mild to moder- only a precaution. Doses of sildenafil greater than ate hepatic impairment being considered for ta- 25mg administered with an alpha-blocker may dalafil therapy should not exceed 10 mg of tadala- lead to symptomatic hypotension and therefore fil daily. On the other hand, tadalafil use is not should not be taken within 4 hours of alpha- recommended in patients with severe hepatic im- blocker. A 25 mg dose of sildenafil may be taken Drug Interactions
Vardenafil has also been shown to have the po- tential for QTc prolongation. As a result of this CYP 3A4 inhibitors, such as ketoconazole, itra- possibility, patients with congenital QTc prolonga- conazole, erythromycin, ritonavir, indinivir, have tion and those taking Class IA or III antiarryhthmic been shown to increase concentrations of all of medications or other medications known to pro- the PDE5 inhibitors. As a result, dosage adjust- long the QT interval should avoid using vardenafil. ments are required for all PDE5 inhibitors when administered concurrently with a CYP 3A4 inhibi- Special Populations
Elderly: When using sildenafil, a starting dose of Adverse Reactions
25 mg should be considered because of de- creased clearance of the drug. For vardenafil, a The most common adverse effects reported for all starting dose of 5 mg should be considered. No 3 agents included headache, dyspepsia, flushing, dose adjustment is required for elderly patients and nasal congestion. Back pain and myalgia were also a common adverse effect associated with the use of tadalafil because of its increased Renal Impairment: No dosage adjustment is affinity for the PDE11 receptor as compared to the needed in patients with mild (CrCl 50 to 80 mL/ other 2 drugs. Tadalafil and vardenafil display min), moderate (CrCl 30 to 50 mL/min), or severe less inhibitory effects toward the PDE6 isoform as renal impairment (CrCl <30 mL/min) with the use compared to sildenafil. This isoform is found in of vardenafil. The use of vardenafil, however, has the eye and possibly explains the increased not been evaluated in patients on dialysis. In re- chance of abnormal vision with the use of silde- gards to sildenafil, the pharmacokinetics were not nafil as compared to vardenafil or tadalafil. Robert C. Byrd Health Sciences Center of West Virginia University Charleston Division
mended in patients with underlying heart con- Mechanism of Action: Penile erection during
3. These drugs should be taken about an hour sexual stimulation occurs as a result of an in- before anticipated sexual activity. In addition, crease in blood flow to the penis. Sexual stimula- the effects of tadalafil may last up to 36 hours. tion itself relies on the release of nitric oxide (NO). 4. These drugs should generally not be taken NO stimulates the synthesis of cGMP producing more than once daily. Other medical condi- smooth muscle relaxation in the corpus caverno- tions or medications being taken may warrant sum. As a result of this relaxation, blood flow is a larger time interval between doses, so inform increased into the penis producing an erection. your physician of your preexisting conditions This class of drugs works to inhibit the action of phosphodiesterase type 5 (PDE5), the enzyme 5. Sexual stimulation is still required for all of responsible for the degradation of cGMP. The inhibition of PDE5, therefore, ultimately leads to 6. In the event of an erection that lasts longer an increase in cGMP. Although these drugs in- than 4 hours, the patient should seek immedi- crease cGMP, sexual stimulation is still required to achieve an erection since it is dependent on the 7. Inform physicians if you are taking alpha- blockers, such as prazosin or doxazosin, be-
Absorption/Distribution: All 3 PDE5 inhibitors
are rapidly absorbed with onsets of action of less 8. The use of sildenafil, vardenafil, or tadalafil than an hour following oral administration. Silde- does not protect against sexually transmitted nafil has a bioavailability of about 40% and varde- nafil 15%. Maximum plasma concentrations are 9. Inform your physician of any other medical reached with sildenafil and vardenafil within 30 to conditions you have or any other medications 120 minutes and tadalafil within 2 hours. When you are taking before considering starting a sildenafil is taken with a high fat meal, the rate of absorption is reduced with a mean delay in Tmax of 60 min. The mean steady state Vd (Vss) for References
sildenafil is 105 L. The rate of absorption is also 1. Levitra® (vardenafil) prescribing information. Bayer reduced with the administration of vardenafil fol- Pharmaceuticals. West Haven, CT. August 2003. lowing a high fat meal causing a reduction of 2. Cialis® (tadalafil) prescribing information. Eli Lilly. Cmax of 18-50%. The mean Vss for vardenafil is 208 L. The rate and extent of absorption of ta- 3. Viagra® (sildenafil) prescribing information. Pfizer. dalafil is not influenced by food and it has a Vss of 4. Gressor U, Gleiter CH. Erectile dysfunction: com- parison of efficacy and side effects of the PDE-5 inhibi- Metabolism/Excretion: Sildenafil and vardenafil
tors sildenafil, vardenafil, and tadalafil. Review of the are predominantly metabolized by liver through literature. Eur J Med Res 2002;7:435-46. the CYP3A4 isozyme and to a minor extent by 5. The Food and Drug Administration. FDA approves CYP2C9. Tadalafil is predominately metabolized new drug for treatment of erectile dysfunction in men. through the CYP3A4 pathway. Sildenafil and FDA Talk Paper. 2003 Aug 19. http://www.fda.gov/bbs/ vardenafil both have half-lives of approximately 4 topics/ANSWERS/2003/ANS01249.html. [Accessed hours, while tadalafil has a half life of about 18 hours and duration of effect of up to 36 hours. All 6. Palacioz K. New drug: Levitra (vardenafil). Pharma- 3 drugs are excreted predominantly in the feces 7. Wienkes R. New drug: Cialis (tadalafil). Pharma- Patient Information
8. Hellstrom WJ, Gittelman M, Karlin G, et al. Vardenafil for treatment of men with erectile dysfunction: 1. These drugs can cause your blood pressure to efficacy and safety in a randomized, double-blind, drop suddenly. Do not take these drugs with placebo-controlled trial. J Androl 2002;23:163-71. 9. Husser DA. The phosphodiesterase type 5 (PDE5) 2. There is a potential cardiac risk with sexual inhibitors for erectile dysfunction. Facst and Compari- activity. The use of these drugs is not recom- A Primary Care Physician’s Guide to Newly Released Medications
duloxetine in pain management. One such
Cymbalta® (duloxetine hydrochloride)
study indicated that duloxetine therapy pro-
vided significant improvement in pain when

Nicholas Ball, Pharm.D. Candidate
compared with placebo, with nearly 50% of the
improvement being unrelated to improvement
in depression. Pain was assessed using the
Somatic Symptom Inventory and Visual Ana-
log Scales. Pain improvement which did not
correlate to improvement in HAM-D-17 scores
indicated pain relief independent of antide-
pressant action. The improved pain also re-
lated into an increased estimation of remis-

sion. Another study determined that not only
Cymbalta® [duloxetine hydrochloride (doo-LOX-e- did duloxetine provide greater relief from pain
teen)], a selective serotonin and norepinephrine symptoms than placebo, but also exhibited a
reuptake inhibitor (SSNRI), was approved for the 44% remission estimation in comparison to
treatment of major depressive disorder in August the 16% estimation for placebo. These results
2004. Duloxetine offers significant relief from the of pain management can be extrapolated to
symptoms of depression, pain in particular, which the relief of pain associated with diabetic neu-
led to its approval for the treatment of diabetic pe- ropathy. A study in which patients with dia-
ripheral neuropathy in September 2004. Duloxet- betic neuropathy received three random doses
ine is the only medication currently approved for of duloxetine, 20 mg QD, 60 mg QD, and 60 mg
the treatment of pain associated with diabetic neu- BID tested this hypothesis. The patients re-
ropathy. Duloxetine is the second member of the ceiving the 60 mg doses achieved improve-
class of SSNRIs alongside Effexor® (venlafaxine) ment in pain symptoms within one week. The
results of this trial contributed to the approval
of duloxetine for diabetic neuropathy. No
Therapeutic Recommendation
studies specifically comparing the efficacy of
duloxetine to other agents for diabetic neu-
Duloxetine has demonstrated efficacy in com-
ropathy exist to date.

parison to selective serotonin reuptake inhibi-
In clinical trials for use in stress urinary incon-
tors (SSRIs), the current first-line treatment for
tinence (SUI), duloxetine exhibited improve-
depression. A study comparing duloxetine to
ment in symptoms versus placebo (p=0.05),
fluoxetine (Prozac®) and placebo demon-
and demonstrated improvement in quality of
strated duloxetine to offer significant improve-
life (p=0.007). One study demonstrated a 50%
ment in the primary outcome, improvement in
decrease in incontinence episodes with du-
17-item Hamilton Depression Rating Scale
loxetine versus 27% with placebo (p<0.001).
(HAM-D-17) scores, over placebo. An estimate
Currently SUI is an off-label use, with no FDA
of the rate of remission of depression was
approval of duloxetine for this indication.
higher with duloxetine (43%), than both
fluoxetine (30%) and placebo (27%). Another
Dosing and Administration
study comparing the efficacy of duloxetine to
paroxetine (Paxil®) and placebo also used im-
Duloxetine is available as 20 mg, 30 mg, and 60 provement in the HAM-D-17 score as the pri-
mg capsules. The recommended dosage range mary outcome measure. Duloxetine exhibited
for major depressive disorder is 40 mg (in two di- superior results to both placebo and paroxet-
vided doses of 20 mg) up to 60 mg (in two divided ine with an improvement in the HAM-D-17 of
doses of 30 mg or once daily). The recommended 2.43 points, compared to placebo and 2.39
dosage for pain associated with diabetic periph- points compared to paroxetine. The study
eral neuropathy is 60 mg daily, although doses as also demonstrated a greater reduction in pain
high as 120 mg daily have been demonstrated to symptoms with duloxetine compared to pla-
be safe. Doses higher than 60 mg daily have demonstrated no added benefit. A low starting Several studies have investigated the role of
dose should be considered in all patients in order Robert C. Byrd Health Sciences Center of West Virginia University Charleston Division
to assess tolerability of side effects before in- Concomitant Illness: Information regarding the use of duloxetine concurrently with other medical conditions is limited. Caution should be used Contraindications
when concurrent medical conditions are present. Duloxetine is contraindicated in patients with a known hypersensitivity to duloxetine or to any Cost Comparison
component in the formulation. Patients taking monoamine oxidase inhibitors should not take du- Medication/Dose
loxetine. Use caution with patients who have un- controlled narrow-angle glaucoma, and avoid if Depression
The FDA has issued a warning concerning the use of antidepressants with pediatric and adoles-cent patients regarding an increased risk of sui- cide. Duloxetine use has not been evaluated in Effexor XR® (venlafaxine)
pediatric and adolescent patients. Adults can ex- perience suicidal ideation as well. It is recom-mended that any patient receiving antidepressant medication be closely monitored for worsening in depressive symptoms. Prior to initiation of antide- Diabetic Neuropathy
pressant therapy patients should be screened for bipolar disorder in order to prevent the occurrence of a manic or hypo-manic episode. Precautions and Contraindications
Hepatotoxicity: Duloxetine can elevate the levels of liver enzymes and bilirubin. Alcohol may in- crease the chance of liver damage. Duloxetine is not recommended in patients with any hepatic im- Blood Pressure: Duloxetine has been associated with increases in both diastolic and systolic blood * Price represents 30 days of therapy at cost to the patient.
pressures. Average systolic increases of 2 mmHg and average diastolic increases of 0.5 mmHg Special Populations
have been the most commonly observed. Meas- Renal Impairment: Data regarding duloxetine and urements of blood pressure should be obtained decreased renal function is limited; however, pa- prior to treatment as well as throughout the course tients undergoing chronic intermittent hemodialy- sis demonstrated much higher levels of duloxetine Seizure Disorder: Duloxetine has not been evalu- than normal renal function patients. Metabolites ated in patients with seizure disorders. Use of du- also increased seven to nine fold in renally im- loxetine in this population should be carefully paired patients. Duloxetine is not recommended monitored due to the potential for seizure develop- in patients with severe renal dysfunction (CrCl<30 Discontinuation of Treatment: A tapered decrease Hepatic Impairment: Patients exhibiting hepatic in dose is recommended rather than abruptly halt- impairment have a diminished duloxetine metabo- ing treatment due to the potential for withdrawal lism and elimination. The half-life of duloxetine effects such as dizziness, nausea, vomiting, anxi- hydrochloride is extended nearly three times greater in patients with hepatic impairment. Du- Robert C. Byrd Health Sciences Center of West Virginia University Charleston Division
loxetine is not recommended in this population. Smoking Status: The bioavailability of duloxetine Absorption/Distribution: Upon oral administration is decreased approximately one-third the normal duloxetine is readily absorbed with peak concen- level in patients who smoke. No dosage adjust- trations achieved in about 6 hours. Food delays absorption from 6 to 10 hours and can decrease absorption by 10%. The average volume of distri- Age: Data suggests that the half-life is somewhat bution of duloxetine is 1640 L and it is highly pro- increased with age; however, no difference was detected in safety or efficacy with regards to age. Dosage adjustments relative to age are not essen- Metabolism/Excretion: Duloxetine undergoes widespread metabolism to several different me- Pregnancy and Lactation: Duloxetine is rated tabolites. The majority of duloxetine metabolism Category C for pregnancy. Duloxetine should be used only when the potential benefit outweighs zymes in the liver. Roughly 70% of duloxetine is the harm. Duloxetine is not recommended while eliminated in the urine in the form of metabolites with approximately 20% being eliminated in the Drug Interactions
Duloxetine is an inhibitor of CYP2D6, thus medi- Patient Information
should be used with caution due to the potential 1. The medication may be taken with our without for duloxetine to alter the medications’ effects. Inhibitors of both CYP1A2 and CYP2D6 have the 2. Patients and caregivers should be aware for potential to increase duloxetine levels. Duloxetine signs of anxiety, panic attacks, insomnia, irrita- should be used with caution with these medica- bility, hypomania, mania, worsening symp- tions. Some common CYP1A2 inhibitors include toms, and suicidal thoughts. These symptoms cimetidine, ciprofloxacin, clarithromycin, and etha- are of particular importance if discovered early nol. Some common CYP2D6 inhibitors include in treatment. Such symptoms should be re- SSRIs, ranitidine, tricyclic antidepressants, and ported to the physician or pharmacist as soon 3. Inform physician and pharmacist of all medica- Common Adverse Effects
tions taken, this includes prescription and non- prescription medications, as well as nutritional The most common adverse effects reported dur- ing clinical trials involving duloxetine were gastro- 4. Swallow capsules whole. Crushing, chewing, intestinal symptoms such as nausea, dry mouth, or sprinkling the capsules on food may cause constipation, and somnolence. Less common side effects reported were sexual side effects, in- 5. Use caution if operating heavy machinery or creased liver enzyme values, increased blood driving until the effects of the medication can 6. Patients who use excessive amounts of alco- Pharmacology
hol should avoid duloxetine due to an in- Mechanism of Action: Serotonin (5HT) and nore- pinephrine are two neurotransmitters in which de- creased levels are believed to play an important role in the development of several psychiatric dis-orders, depression in particular. Painful symp-toms of depression may also be related to the pathways of these two neurotransmitters. Du-loxetine hydrochloride selectively inhibits norepi-nephrine and 5HT from binding to their receptors thus allowing a build-up of both norepinephrine Robert C. Byrd Health Sciences Center of West Virginia University Charleston Division
1. Cymbalta® (duloxetine hydrochloride) product information insert. Eli Lilly and Co, Indianapolis, IN. September
2. Goldstein DJ, Mallinckrodt C, Lu Y, and Demitrack MA. Duloxetine in the treatment of major depressive disor-
der: a double-blind clinical trial. J Clin Psychiatry. 2002;63(3):225-231
3. Goldstein DJ, Lu Y, Detke MJ, et al. Duloxetine in the treatment of depression: a double-blind placebo-
controlled comparison with paroxetine. J Clin Psychopharmacology. 2004;24(4):389-399.
4. Fava M, Mallinckrodt C, Detke MJ, et al. The effect of duloxetine on painful physical symptoms in depressed
patients: do improvements in these symptoms result in higher remission rates? J Clin Psychiatry. 2004;65(4):521-
5. Detke MJ, Lu y, Goldstein DJ, et al. Duloxetine, 60 mg once daily, for major depressive disorder: a randomized
double-blind placebo-controlled trial. J Clin Psychiatry. 2002;63(4):308-315.
6. Delgado PL. Common pathways of depression and pain. J Clin Psychiatry. 2004;65(suppl 12):16-19
7. Millard RJ, Moore K, Rencken R, et al. Duloxetine vs placebo in the treatment of stress urinary incontinence: a
four-continent randomized clinical trial. BJU Int. 2003;93:311-318.
8. Dmochowski RR, Miklos JR, Norton PA, et al. Duloxetine versus placebo for the treatment of North American
women with stress urinary incontinence. J Urology. Oct. 2003;179:1259-1263. Visit New Drug Update online at: www.hsc.wvu.edu/charleston/sopc/nduhome.html
Departments of Internal Medicine and Clinical Pharmacy 3110 MacCorkle Ave., SE Charleston, WV 25304

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Biochemical and Biophysical Research Communications 336 (2005) 1144–1149Induction of tamoxifen resistance in breast cancer cellsRainer Girgert a,*, Hartmut Schimming b, Wolfgang Ko¨rner c, Carsten Gru¨ndker a,a Department of Obstetrics and Gynecology, University of Go¨ttingen, D-37099 Go¨ttingen, Germanyb Facility for Electronic Equipment, University of Ulm, D-89075 Ulm, Germanyc Bava

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Alcohol/Drug Abuse Adamson, S. J., & Sellman, J. D. (2001). Drinking goal selection and treatment outcome in out-patients with mild-moderate alcohol dependence. Drug and Alcohol Review, 20 , 351-359. Agostinelli, G., Brown, J. M., & Miller, W. R. (1995). Effects of normative feedback on consumption among heavy drinking college students. Journal of Drug Education, 25 , 31-40. Al

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