Antidepressants addiction

Despite public misconceptions, there is little firm evidence that the typical and atypical antidepressants produce dependence in clinical users. A review of 21 case reports of antidepressant addiction revealed that 12 were associated with tranylcypromine, although 8 of these 12 had a previous history of substance misuse (Haddad, 1999). Tranylcypromine s structural similarity to amphetamine may account for the significant number of reports of its addictive potential, but even here the term (mild) discontinuation reaction rather than withdrawal reaction should be used to allay any concerns patients might have (Haddad, 1999). 

Cocaine and desipramine inhibit the reuptake of monoamine neurotransmitters whereas amphetamine, which is a phenylalkylamine - similar in structure to the catecholamines, see Fig. 4 - competes for uptake and more importantly, evokes efflux of the monoamine neurotransmitters. All of them exert antidepressant effects. Cocaine and amphetamine are addictive whereas tricyclic antidepressants and their modern successors are not. The corollaty of the addictive properties is interference with DAT activity. Blockade of DAT by cocaine or efflux elicited by amphetamine produces a psychostimulant effect despite the different mechanisms even the experienced individual can hardly discern their actions. Because of the risk associated with inhibiting DAT mediated dopamine clearance the antidepressant effects of psychostimulants has not been exploited. 

In general, with the exception of the central role that benzodiazepines play in the treatment of alcohol withdrawal, the use of medications that have been approved for alcoholism rehabilitation remains very limited. A survey of nearly 1,400 addiction physicians showed that they prescribed disulfiram to only 9% of their alcoholic patients and that naltrexone was prescribed for only slightly higher proportion of patients (13%) (Market al. 2003). These tesults contrast with findings for antidepressants, which were prescribed to 44% of alcoholic patients. Although neatly all of these physicians had heatd of both disulfiram and naltrexone, their self-reported level of knowledge of these medications was much lowet than that of antidepressants. 

Ciraulo DA, Jaffe JH Tricyclic antidepressants in the treatment of depression associated with alcoholism. Clin Psychopharmacol 1 146—150, 1981 Ciraulo DA, Nace E Benzodiazepine treatment of anxiety or insomnia in substance abuse patients. Am J Addict 9 276—284, 2000 Ciraulo DA, Barnhill JG, Jaffe JH, et al Intravenous pharmacokinetics of 2-hydroxy-imipramine in alcoholics and normal controls. J StudAlcohol 51 366-372, 1990 Ciraulo DA, Knapp CM, LoCastro J, et al A benzodiazepine mood effect scale reliability and validity determined for alcohol-dependent subjects and adults with a parental history of alcoholism. Am J Drug Alcohol Abuse 27 339—347, 2001 Collins MA Tetrahydropapaveroline in Parkinson s disease and alcoholism a look back in honor of Merton Sandler. Neurotoxicology 25 117-120, 2004 COMBINE Study Research Group Testing combined pharmacotherapies and behavioral interventions in alcohol dependence rationale and methods. Alcohol Clin Exp Res 27 1107-1122, 2003a... 

Anxiety disorders are common in the population of opioid-addicted individuals however, treatment studies are lacking. It is uncertain whether the frequency of anxiety disorders contributes to high rates of illicit use of benzodiazepines, which is common in methadone maintenance programs (Ross and Darke 2000). Increased toxicity has been observed when benzodiazepines are co-administered with some opioids (Borron et al. 2002 Caplehorn and Drummer 2002). Although there is an interesting report of clonazepam maintenance treatment for methadone maintenance patients who abuse benzodiazepines, further studies are needed (Bleich et al. 2002). Unfortunately, buspirone, which has low abuse liability, was not effective in an anxiety treatment study in opioid-dependent subjects (McRae et al. 2004). Current clinical practice is to prescribe SSRIs or other antidepressants that have antianxiety actions for these patients. Carefully controlled benzodiazepine prescribing is advocated by some practitioners. 

Kranzler HR, Bauer LO, Hersh D, et al Carbamazepine treatment of cocaine dependence a placebo-controlled trial. Drug Alcohol Depend 38 203-211, 1995 Levin FR, Lehman AF Meta-analysis of desipramine an adjunct in the treatment of cocaine addiction. J Clin Pharmacol 11 374-378, 1991 Lima MS, Reisser AA, Soares BG, et al Antidepressants for cocaine dependence. Cochrane Database Syst Rev 4 CD002950, 2001 Ling W, Shoptaw S, Majewska D Baclofen as a cocaine anti-craving medication a preliminary clinical study 0etter). Neuropsychopharmacology 18 403 04, 1998... 

The reason for this warning is that abrupt cessation of SSRIs produces withdrawal symptoms in about 20 per cent of patients. Symptoms of withdrawal from antidepressant medication include gastrointestinal disturbances (abdominal cramping and pain, diarrhoea, nausea and vomiting), flu-like symptoms, headaches, sleep disturbances, dizziness, blurred vision, numbness, electric-shock sensations, twitches and tremors. Abrupt withdrawal can also produce symptoms of depression and anxiety, which can occur within hours of the first missed dose of the drug.11 Withdrawal symptoms are sometimes mistaken for a relapse, leading patients to resume antidepressant medication and to conclude that they need it in order to remain free of depression. Technically, this is not considered addiction , but it does seem awfully close. 

Amphetamine Clinically used for narcolepsy (sudden day-time onset sleep) and Attention Deficit Hyperactivity Disorder (ADHD) formerly used as a short-term slimming agent, as an antidepressant and to boost athletic performance recreational use widespread tolerance develops readily highly addictive regular users suffer many health problems and a reduced life expectancy amphetamine psychosis may develop, with similar symptoms to acute paranoid schizophrenia. 

Haddad P (1999). Do antidepressants have potential to cause addiction Journal of Psychopharmacology, 13, 300-307. 

Nicotine is responsible for the highly addictive properties of tobacco products. Addiction occurs in 30% of those who experiment with tobacco products, and more than 80% of those who attempt to quit smoking will relapse within a year. Withdrawal from nicotine produces a syndrome characterized by nicotine craving as well as dysphoria, anxiety, irritability, restlessness and increased appetite. It is treated with nicotine replacement therapies, such as nicotine gum and patches, and/or with buproprion, a drug that is classified as an antidepressant but has multiple and complex effects in brain. Buproprion reduces craving in some smokers. Nicotine addiction has been reviewed recently at cellular and systems levels [38-41]. 

TDM has improved the performance of anticancer, antidementia, antidepressant, antiepileptic, anticonvulsant, antifungal, antimicrobial, antipsychotic, antiretroviral, anxiolytic, hypnotic, cardiac, addiction treatment, immunosuppressant, and mood stabilizer drags for more than 30 years.2-9 Many analytical procedures evolved as analytical techniques and instrumentation have advanced. This chapter briefly reviews the different types of analytical methods the applications of high-throughput techniques in TDM are discussed in detail. 

The most commonly used therapies for anxiety and depression are selective serotonin reuptake inhibitors (SSRIs) and the more recently developed serotonin noradrenaline reuptake inhibitors (SNRIs). SSRIs, which constitute 60% of the worldwide antidepressant and antianxiety market, are frequently associated with sexual dysfunction, appetite disturbances and sleep disorders. Because SSRIs and SNRIs increase 5-HT levels in the brain, they can indirectly stimulate all 14 serotonergic receptor subtypes [2,3], some of which are believed to lead to adverse side effects associated with these drugs. Common drugs for short-term relief of GAD are benzodiazepines. These sedating agents are controlled substances with addictive properties and can be lethal when used in combination with alcohol. The use of benzodiazepines is associated with addiction, dependency and cognitive impairment. 

Once a methamphetamine addict stops taking the drug, the withdrawal symptoms can be very severe and include depression and anxiety, increased appetite, fatigue, paranoia, irritability, aggressive behavior, and intense craving for the drug. Some of these symptoms can be eased with sedative drugs like Valium or antidepressants like Prozac . 

Bupropion is another alternative pharmacological approach to tobacco abstinence. It is an antidepressant drug that blocks reuptake of norepinephrine and dopamine, and also blocks nicotinic receptors in the low to intermediate micromolar range (Fryer and Lukas 1999). Thus, the effects of bupropion on nicotine addiction may be through dual effects on dopaminergic and nicotinic systems. Further, it has been an effective treatment in controlled studies, both alone and in combination with the nicotine patch. Bupropion alone or in combination with a nicotine patch was more effective than placebo or the nicotine patch alone. 

One popular miscouception is that modem autidepressauts also induce euphoria. This is not true. Autidepressauts do not lift the mood of nondepressed individuals. Antidepressants simply relieve depression and hopefully return a person to a normal euthymic mood. The lone exception is the bipolar patient who may have a manic episode triggered by taking an antidepressant without a mood stabilizer. Because antidepressants do not produce pleasurable euphoric feelings in nondepressed people, they are not addictive. 

Monoamine Oxidase inhibitors (MAOis). Developed in the 1950s, the MAOIs were the first class of antidepressants. Subsequently, in the 1960s, the MAOis were also found to be effective anxiolytics. Unlike benzodiazepines and barbiturates, the MAOis are not addictive however, their onset of action is delayed not by minutes or hours but by 3 weeks or more. 

Tricyclic Antidepressants (TCAs). The TCAs were also introduced in the 1950s, and some were discovered to be effective anxiolytics in the 1960s. For example, early studies pioneered by Donald Klein and his colleagues indicated that imipra-mine (Tofranil) effectively relieved panic attacks. Like the MAOIs, the TCAs are not addictive but also require over 3 weeks to begin to achieve significant therapeutic benefit for anxiety. 

Azapirones. Though several azapirones have been developed and tested in the laboratory setting, only one, bnspirone (Bnspar), is currently on the market. Buspirone is the first nonsedating, nonbenzodiazepine anxiolytic, other than the antidepressants described earlier. It has no dependence or addictive liability and is not lethal in overdose. Buspirone is also devoid of many of the problems of the benzodiazepines such as sedation, motor impairment, addiction, physical dependence, or withdrawal. Yet, doubts remain in the minds of many practitioners regarding the effectiveness of buspirone. This will be discussed in more detail later in this chapter. 

Antidepressants. The tricyclic antidepressant desipramine has shown some small success in reducing cocaine craving, but the results are not overly impressive, and desipramine has many well-documented side effects and is dangerous in overdose (see Chapter 3 for more information). Cocaine-abusing patients who are not highly motivated will usually not remain adherent to the desipramine prescription. We do not recommend desipramine for the nondepressed cocaine addict. 

Although not an antidepressant also varenicline can be mentioned here. It is the first nicotinic receptor partial agonist approved to treat smoking addiction. As a partial agonist, it both reduces cravings for and decreases the pleasurable effects of cigarettes and other tobacco products. 

Within this Held, most of the research and results have been focused on the effects of drug therapy on the disorders induced by alcohol, and by the abuse of opiates. For a broader discussion of substance abuse see Chapter 18. In all instances of alcohol or drug abuse the first objective is to wean the patients from the addictive substance, treating or preventing the effects of withdrawal for those substances which cause physical dependence (alcohol, nicotine, opiates, caffeine, certain psychotropic agents such as benzodiazepines, possibly antidepressants). The second phase is the prevention of recurrence or relapse, which relies on a combination of social support, psychotherapy, and pharmacotherapy where available. In this respect, alcoholism is exemplary. 

Despite the success of bupropion for depression, there has been little progress or apparent interest in antidepressants focused on dopaminergic activity or potentiation. The impact of more dopaminergic medications can be inferred from the unique clinical uses of bupropion for depression, nicotine addiction, ADFID... 

The use of benzodiazepines in anxiety disorders represents a difficult issue because of the well-known addictive properties of this substance class furthermore, the depressogenic lability of benzodiazepines represents a major problem in the treatment of generalized anxiety disorders, in which concomitant depressive symptoms occur in up to 50% of patients [Gulley and Nemeroff 1993 Rickels and Schweizer 1993]. Therefore, a compound mimicking endogenous anxiolytic effects, and that might further possess potential antidepressive properties, is warranted. Neuroactive steroids could represent such a substance class. However, the following issues need to be addressed in this respect ... 

Discontinuation of antidepressant medication should be concordant with the guidelines for treatment duration (see Acute Major Depression subsection in the preceding section). It is advisable to taper the dose while monitoring for signs and symptoms of relapse. Abrupt discontinuation is also more likely to lead to antidepressant discontinuation symptoms, often referred to as withdrawal symptoms. The occurrence of these symptoms after medication discontinuation does not imply that antidepressants are addictive. 

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