Treatment obsessive-compulsive disorder

SSRIs are well tolerated. Adverse effects for compounds in this class include nervousness, tremor, dizziness, headache, insomnia, sexual dysfunction, nausea, and diarrhea. In addition, the tricycHc antidepressant clomipramine (33), which is a potent nonselective serotonin reuptake inhibitor, is approved for treatment of obsessive—compulsive disorder. 

SSRIs are widely used for treatment of depression, as well as, for example, panic disorders and obsessive—compulsive disorder. These dmgs are well recognized as clinically effective antidepressants having an improved side-effect profile as compared to the TCAs and irreversible MAO inhibitors. Indeed, these dmgs lack the anticholinergic, cardiovascular, and sedative effects characteristic of TCAs. Their main adverse effects include nervousness /anxiety, nausea, diarrhea or constipation, insomnia, tremor, dizziness, headache, and sexual dysfunction. The most commonly prescribed SSRIs for depression are fluoxetine (31), fluvoxamine (32), sertraline (52), citalopram (53), and paroxetine (54). SSRIs together represent about one-fifth of total worldwide antidepressant unit sales. 

Doxepin [1668-19-5] (38), unlike other commercially available tricyclics, has an oxygen atom in the bridge between the two aromatic rings. It is marketed as a cis—trans mixture (1 5) of isomers, both of which are active. This close relative of amitriptyline (33) has both sedative and anxiolytic properties associated with its antidepressant profile. Maprotiline [10262-69-8] (39) and amoxapine [14028-44-5] (40) are pharmacologically, although not chemically, similar to the tricycHc secondary amines. Clomipramine [303-49-1] (41) has similar pharmacological and antidepressant efficacy. However, clomipramine is approved by the U.S. FDA only for the treatment of obsessive—compulsive disorder. Representative brands of tricycHc antidepressants marketed in the United States are Hsted in Table 2. 

Antidepressants are small heterocyclic molecules entering the circulation after oral administration and passing the blood-brain barrier to bind at numerous specific sites in the brain. They are used for treatment of depression, panic disorders, generalized anxiety disorder, social phobia, obsessive compulsive disorder, and other psychiatric disorders and nonpsychiatric states. 

Antidepressant drugs are used to manage depressive episodes such as major depression or depression accompanied by anxiety. These drugs may be used in conjunction with psychotherapy in severe depression. The SSRIs also are used to treat obsessive-compulsive disorders. The uses of individual antidepressants are given in the Summary Drug Table Antidepressants. Treatment is usually continued for 9 months after recovery from the first major depressive episode. If the patient, at a later date, experiences another major depressive episode, treatment is continued for 5 years, and with a third episode, treatment is continued indefinitely. 

The enantiomerically pure 3-arylglutaric ester are precursors for the synthesis of (—)-paroxetine [10], a selective serotonin reuptake inhibitor used in the treatment of depression, obsessive compulsive disorder, and panic, and (i )-Baclofen [11], a GABAb receptor agonist, which is used cHnically in the treatment of spasticity (Chart 5.1). 

Extrapolation to other countries is not easy. Canada has a very different health-care system to the USA. A small-scale study involving 466 anxiety disorder patients in Quebec established a clear relationship between the severity of the disorder and utilization of health services (McCusker et al, 1997). Patients with obsessive-compulsive disorder were particularly likely to seek treatment. No information on dmg use was presented. 

Greist JH, Bandelow B, Hollander E, et al. Long-term treatment of obsessive-compulsive disorder in adults. CNS Spectr 2003 8(Supplement 1) 7-16. 

Hollander E, Bienstock CA, Koran LM, et al. Refractory obsessive-compulsive disorder state-of-the-art treatment. J Clin Psychiatry 2002 63(Supplement 6) 20-29. 

Husted DS, Shapira NA. A review of the treatment for refractory obsessive-compulsive disorder from medicine to deep brain stimulation. CNS Spectr 2004 9 833-847. 

Appropriate management of AN also requires the early detection and treatment of any comorbid psychiatric disorders. The most common comorbid conditions associated with AN are major depressive disorder (MDD), obsessive-compulsive disorder (OCD), and substance use disorders. At the time of presentation, over 50% of AN patients also fulfill criteria for MDD however, accurate diagnosis of depression in these patients is complicated by the fact that prolonged starvation often produces a mood disturbance and neurovegetative symptoms identical to MDD. If MDD appears to be comorbid with AN at the time of presentation, there is debate as to whether it is more prudent to withhold treatment of the depression until weight restoration has been initiated. If the depression persists despite refeeding, then treatment of the depression is likely warranted. 

In addition to their proven efficacy in the treatment of all types of depression, the SSRIs have been shown to be the drugs of choice in the treatment of panic disorder, obsessive-compulsive disorder, bulimia nervosa, and as an adjunct to the treatment of alcohol withdrawal and relapse prevention, premenstrual dysphoric disorder and post-traumatic stress disorder. The usefulness of these drugs in treating such a diverse group of disorders reflects the primary role of serotonin in the regulation of sleep, mood, impulsivity and food intake. 

Obsessive compulsive disorder in an 8-year-old can be treated using fluvoxamine (selective serotonin reuptake inhibitor, SSRI). It is usually administered initially os 25 mg daily, and increased if necessary in steps of 25 mg every 4-7 days to a maximum of 200 mg daily. If there is no improvement within 10 weeks, treatment should be reconsidered. A selective serotonin reuptake inhibitor should not be started until 2 weeks after stopping a monoamine oxidase inhibitor (MAOl), and conversely a MAOl should not be started until at least a week after an SSRI has been stopped. 

Clomipramine Only for treatment of Obsessive-Compulsive Disorder (OCD). 

A considerable number of tricyclic antidepressants have been developed in the past, although with slight differences in their pharmacological activities, ah with similar efficacy. They are primarily indicated for the treatment of endogenous depression. However this does not exclude efficacy in patients in whom the depression is associated with organic disease or in patients with reactive depression or depression combined with anxiety. They may also benefit patients during the depressive phase of manic-depressive disorder. For some also efficacy has been claimed in panic states, phobic disorders, and in obsessive-compulsive disorders. 

In recent years many of these primary care cases that would formerly have been seen as anxiety disorders have been portrayed as anxious-depressives and have led to treatment with antidepressants, in particular the more recent serotonin reuptake inhibitors. As part of this rebranding a variety of states such as panic disorder, post-traumatic stress disorder, social phobia and generalized anxiety disorder have appeared, along with more traditional disorders such as obsessive compulsive disorder (OCD). Many of these diagnoses are likely to lead to prescriptions of an SSRI although the evidence for benefit from SSRIs is poor except for OCD. 

Lesch KP, Hob A, Schulte HM (1991) Long-term fluoxetine treatment decreases 5-HTlA receptor responsivity in obsessive compulsive disorder. Psychopharmacology (Berl) 105 415-420... 

Atmaca M, Kuloglu M, Tezcan E, Gecici O (2002) Quetiapine augmentation in patients with treatment resistant obsessive-compulsive disorder a single-blind, placebo-controlled study. Int Clin Psychopharmacol 17 115-119... 

Jenike MA, Baer L, BaUantine T, Martuza RL, Tynes S, Giriunas 1, Buttolph ML, Cassem NH (1991) Cingulotomyfor refractory obsessive-compulsive disorder. A long-term follow-up of 33 patients. Arch Gen Psychiatry 48 548-555 Kent JM, Mathew SJ, Gorman JM (2002) Molecular targets in the treatment of anxiety. Biol Psychiatry 52 1008-1030... 

Kobak KA, Greist JH, Jefferson JW, Katzelnick DJ, Henk HJ (1998) Behavioral versus pharmacological treatments of obsessive compulsive disorder a meta-analysis. Psychopharmacology (Berl) 136 205-216... 

Antidepressant drugs, such as the tricyclic antidepressants and the selective serotonin reuptake inhibitors (SSRIs), are very important for the treatment of psychotic depression (see Chapter 34). They have been shown to be effective when used in the treatment of several anxiety disorders, including general anxiety, obsessive-compulsive disorder, and several phobias, including agoraphobia. Because the SSRIs are less toxic than the tricyclic antidepressants, their use in the treatment of anxiety is safer and less likely to produce serious side effects. 

In 1987, the FDA approved the drug fluoxetine (Prozac) for use in the treatment of major depression. Fluoxetine belongs to a class of agents referred to as selective serotonin reuptake inhibitors (SSRIs). The SSRIs now include sertraline (Zoloft), fiuvoxamine (Luvox), paroxetine (Paxil), and citalopram (Celexa). Fiuvoxamine is approved for use only in obsessive-compulsive disorder and is not discussed in this chapter. 

Clomipramine (Anafranil) also a member of the tricyclic family, possesses similar pharmacology and antidepressant efficacy. This agent, however, has Food and Drug (FDA) approval only for use in the treatment of obsessive-compulsive disorder and is not included in this discussion of antidepressant drugs. 

Unlabeled Uses Treatment of alcohol abuse, dementia, diabetic neuropathy, obsessive-compulsive disorder, panic disorder, smoking cessation... 

Bergqvist, P.B., Bouchard, C., and Blier, P. (1999) Effect of long-term administration of antidepressant treatments on serotonin release in brain regions involved in obsessive-compulsive disorder. Biol Psychiatry 45 164-174. 

Hanna, G.L. (2000) Clinical and family-genetic studies of childhood ohsesslve-compulslve disorder. In Goodman, W.K., Rudorfer, M.V., and Maser, J.D., eds. Obsessive-Compulsive Disorder Contemporary Issues in Treatment. Mahwah, NJ Lawrence Erl-haum Associates, pp. 87-103. 

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