Drug Dependence and Abuse

Another subject, clearly within the notion of safety, is the assessment of a novel substance s potential to be abused or to induce dependence. These topics are mentioned briefly in ICH S7A, other organ systems . A much more detailed list of recommendations has been made for FDA purposes, but has never been officially adopted (Bigelow 1991). 

Studies assessing dependence or abuse liability are, in principle, required only for drugs acting on the CNS. Candidates for particular attention are psycho- 

The following section describes protocols for evaluating both dependence and abuse. For reasons of homogeneity with the other procedures presented above, only protocols in the rat will be presented. Although results in the rat are generally similar to those obtained in non-human primates, the regulatory authorities, in particular the FDA, prefer primate studies for abuse evaluation because of a presumed increased predictability to man. The active doses and pharmacokinetics are likely to be closer between human and non-human primates, as are the kinds of overt behavioral effects observed. 

Balster RL (1991) Drug abuse potential evaluation in animals. Brit J Addiction 86 1549-1558 

Bigelow GE (1991) Draft Guidelines for Abuse Liability Assessment. Drug Abuse Advisory Committee, FDA, US Public Health Service 

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One-on-one counseling explores the emotional issues underlying a patient s drug dependence and abuse. Individual psychotherapy is particularly useful when there is also some type of mental disorder, such as depression or an anxiety disorder, along with the drug abuse. 

Drug dependence and abuse potential Radioactive drugs Pediatric studies Other information... 

Drug Dependence and Abuse Potential If the drug is a psychotropic substance or otherwise has abuse potential, a section describing relevant clinical studies and experience and studies in test animals is to be submitted. 

Anorectic drugs lead to drug dependence and abuse... 

Srisurapanont M, Jarusuraisin N, Kittirattanapaiboon P Treatment for amphetamine dependence and abuse. Cochrane Database Syst Rev 4 CD003022, 2001 Srisurapanont M, Ali R, Marsden J, et al Psychotic symptoms in methamphetamine psychotic in-patients. Int J Neuropsychopharmacol 6 347-352, 2003 Substance Abuse and Mental Health Services Administration Overview of Findings From the 2002 National Survey on Drug Use and Health (DHHS Publ No SMA 03-3774). Rockville, MD, Substance Abuse and Mental Health Services Administration, 2003... 

There are pharmacological, social and legal issues to consider in this context of drug dependence and, of course, drug users and abusers vary enormously. A chronic alcoholic is very different from a weekend user of cannabis and any consideration of the topic has to consider legal and social issues as well as pharmacological effects of the drugs. 

When treating anxiety one should of course first treat any reversible medical condition. When pharmacological treatment is necessary SSRI is most often drug of choice. Selective serotonin reuptake inhibitors are both effective and safe. Benzodiazepines that have been widely used are drugs with a relative high risk of adverse effects (see Chapter 4). Risks for dependence and abuse must always be considered for benzodiazepines. 

Drug abuse and dependence Physical and psychological dependence and abuse may occur. 

There are major consequences of alcoholism, from child abuse to domestic or public violence to traffic accidents and from cirrhosis to hypertension. Mean life expectancy of alcohol abusers is around 55 years. Alcohol seems involved in several hundred thousand deaths each year in Europe, with considerable added social and health care costs. This is in clear contrast with the little attention paid to the treatment of alcohol dependence and abuse. It is important to note that there is an increasing knowledge of similar effects on driving etc. from other psychoactive substances, particularly from the seda-tive/tranquillizer drugs and antihistamines. 

CNS side effects include confusion, anxiety, lethargy, nausea and vomiting. GIT related effect is constipation. Other side effects are urinary retention, dry mouth, miosis, dysphoria, hypotension, skin rash, itching and urticaria. Tolerance, drug dependence and drug abuse are the main drawbacks of morphine. 

It is true that Strattera has not been demonstrated to cause dependence and abuse like Ritalin, Adderall, and the other stimulant drugs used to treat ADHD and therefore has not been placed in Schedule II by the DEA. But Strattera is a highly stimulating drug. According to the label for Strattera, as found in the Physicians Desk Reference (2007, p. 1817, Table 1), in the clinical trials used for FDA approval, irritability was reported in 8% of subjects, crying in 2%, and mood swings in 2%. 

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