Obsessive-compulsive disorder antidepressants

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. 

Sertraline is a recent antidepressant that is called a selective serotonin reuptake inhibitor (SSRI). It is chemically unrelated to the older tricyclic antidepressants (see Section 5.3). It works by preventing the movement of the neurohormone serotonin into nerve endings. It can help to improve mood and mental alertness, increase physical activity, and improve sleep patterns. It is prescribed for obsessive-compulsive disorder and obesity. It may offer some advantage over fluoxetine by exhibiting little central nervous system (CNS) action. It has less sedation and anxiety and is shorter acting. 

Like sertraline, these two drugs are selective serotonin reuptake inhibitors. Fluoxetine is prescribed for depression, bulimic binge-eating and vomiting, obsessive-compulsive disorder, obesity, alcoholism, and anorexia among other ailments. Paroxetine is used for depression and obsessive-compulsive disorder. Interestingly the three top antidepressants are chemically unrelated to each other, except for being amines, and are unrelated to earlier tricyclic antidepressants. 

Due to the frequent unwanted effects and, in case of tranylcypromine, the numerous and dangerous interactions MAO-inhibitors are more and more replaced by the much less problematic SSRIs. Compounds belonging to this group are citalopram, escitalopram, fluoxetine, paroxetine and sertraline. They are used clinically in the therapy of depression, bulimia and obsessive-compulsive disorders. All SSRIs show a slow onset of action (1-2 weeks). They may induce insomnia and weight loss. The antidepressant ven-lafaxine inhibits both, serotonin and noradrenaline re-uptake and might therefore additionally induce hypertension. 

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. 

Blier P, de Montigny C (1998) Possible serotonergic mechanisms underlying the antidepressant and anti-obsessive-compulsive disorder responses. Biol Psychiatry 44 313-323 Bonasera SJ, Tecott LH (2000) Mouse models of serotonin receptor function toward agenetic dissection of serotonin systems. Pharmacol Ther 88 133-142 Bonhoeffer T (1996) Neurotrophins and activity-dependent development of the neocortex. Curr Opin Nemobiol 6 119-126... 

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. 

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. 

Mechanism of Action An antidepressant and antiobsessive agent that selectively inhibits neuronal reuptake of serotonin. Therapeutic Effect Relieves depression and symptoms of obsessive-compulsive disorder. 

Mechanism of Action An antidepressant, anxiolytic, and obsessive-compulsive disorder adjunct that blocks the reuptake of the neurotransmitter serotonin at CNS neuronal presynaptic membranes, Increasing its availability at postsynaptic receptor sites. Therapeutic Effect Relieves depression, reduces obsessive-compulsive behavior, decreases anxiety... 

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. 

Joffe RT, Schuller DR An open study of buspirone augmentation of serotonin reuptake inhibitors in refractory depression. J Chn Psychiatry 54 269-271, 1993 Joffe RT, Singer W A comparison of triiodothyronine and thyroxine in the potentiation of tricyclic antidepressants. Psychiatry Res 32 241-251, 1990 Joffe RT, Swinson RP Carbamazepine in obsessive-compulsive disorder. Biol Psychiatry 22 1169-1171, 1987... 

Maura G, Andrioli SC, Cavazzani P S-hydroxytryptaminej receptor sites on cholinergic axon terminals of human cerebral cortex mediate inhibition of acetylcholine release. J Neurochem 58 2334-2337, 1992 Mavissakalian M, Turner SM, Michelson L, et al Tricyclic antidepressants in obsessive-compulsive disorder antiobsessional or antidepressant agents 11. Am J Psychiatry 142 572-576, 1985... 

Note. ECT=electroconvulsive therapy OCD=obsessive-compulsive disorder SSRI=selective serotonin reuptake inhibitor TCA=tricyclic antidepressant MAOI=monoamine oxidase inhibitor. 

During all phases of treatment, education, supportive therapy, and, at times, more specific types of psychotherapy are essential for a satisfactory outcome. For example, interpersonal therapy can complement adequate maintenance antidepressant treatment, possibly diminishing the frequency of episodes (see the section Role of Psychosocial Therapies in Chapter 7), and cognitive-behavioral techniques in combination with antiobsessive agents (e.g., clomipramine) can improve the quality of life for patients with obsessive-compulsive disorder, minimizing time spent on disabling rituals (see the section Obsessive-Compulsive Disorder in Chapter 13). 

The Food and Drug Administration (FDA) has approved clomipramine for the treatment of obsessive-compulsive disorder. Clomipramine is also used in the United States, Europe, Canada, England, and, indeed, most of the world as an antidepressant. In six random-assignment, double-blind studies, this agent was equal in efficacy to standard tricyclics, with a side-effect profile comparable with other TCAs ( Table 7-6). 

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