Obsessive-compulsive disorder SSRIs

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

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. 

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. 

Pharmacologically, a principal point relates to the cost-effectiveness of the newer indications for SSRIs in the less common disorders such as obsessive—compulsive disorder and social phobia. These conditions do place a disproportionate burden on health-care systems, and clinical trials of the newer indications are convincing. However, no cost-effectiveness study has yet been petformed to assess this, and prescribing will continue to be based on individual clinical need. 

Zohar and Insel have suggested that the s)nnptoms of obsessive-compulsive disorder are due to supersensitive 5-HTi-type receptors and that the function of SSRIs such as clomipramine, fluoxetine and the non-selective 5-HT antagonist metergoline owe their efficacy to their ability to reduce the activity of these receptors. 

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. 

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. 

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. 

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. 

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. 

The selective serotonin reuptake inhibitors (SSRI) have been used in adults for a wide variety of disorders, including major depression, social anxiety (social phobia), generalized anxiety disorder (GAD), eating disorders, premenstrual dysphoric disorder (PMDD), post-traumatic stress disorder (PTSD), panic, obsessive-compulsive disorder (OCD), trichotillomania, and migraine headaches. Some of the specific SSRI agents have an approved indication in adults for some of these disorders, as reviewed later in this chapter. The SSRIs have also been tried in children and in adults for symptomatic treatment of pain syndromes, aggressive or irritable ( short fuse ) behavior, and for self-injurious and repetitive behaviors. This chapter will review general aspects of the SSRIs and discuss their approved indications in children and adolescents. 

FDA, Food and Drug Administration GAD, general anxiety disorder OCD, obsessive-compulsive disorder PMDD, Premenstrual dysphoric disorder PTSD, post-traumatic stress disorder SRI, serotonin reuptake inhibitor SSRI, selective serotonin reuptake inhibitor. 

FIGURE 39.2 Treatment algorithm for pediatric obsessive-compulsive disorder (OCD). In adjusting cognitive behavior therapy (CBT), increase frequency or intensity, or alter the setting or format, e.g., have it be home based or day treatment. CMI, clomipramine DMI, desipramine NT, nortriptyline SSRI, selective serotonin reuptake inhibitor (fluoxetine, fluvoxamine, paroxetine, sertraline, citalopram). 

Fluoxetine is manufactured by Eli Lilly under the name Prozac, as a 10-mg green football-shaped tablet or a 20-mg green and white capsule. It was the first SSRI introduced for the treatment of depression and anxiety disorders. Fluoxetine is prescribed for obsessive-compulsive disorder, the eating disorder bulimia nervosa, and panic disorder. 

In the United States, fluvoxamine is only prescribed for the treatment of obsessive-compulsive disorder. It is not structurally related to the previously mentioned SSRIs, but it does have similar actions on serotonin reuptake systems. Fluvoxamine often comes in 50-mg tablets. 

Obsessive-compulsive symptoms. Clozapine has been reported to exacerbate symptoms of obsessive-compulsive disorder, probably because of 5-HT2 antagonism (Ghaemi et al. 1995). If this effect occurs, symptoms are usually controlled with the addition of an SSRI. 

TABLE 13-12. Clomipramine versus standard antidepressants (not SSRIs) for obsessive-compulsive disorder... 

That situation has changed with the development of clomipramine and the SSRIs, which appear to have unique efficacy in treating OCD when compared with other types of psychotropics (see Chapter 13, Obsessive-Compulsive Disorder ). In addition, more effective behavioral approaches have been developed, which, in combination with medication, can substantially ameliorate this condition. 

FIGURE 7—33. Mechanism of action of buspirone augmentation—pact 3. Shown here is how buspirone potentiates ineffective SSRI action at 5HT1A somatodendritic autoreceptors, resulting in the desired disinhibition of the 5HT neuron. This combination of 5HT1A agonists plus SSRIs may be more effective, not only in depression but also in other disorders treated by SSRIs, such as obsessive-compulsive disorder and panic. 

Perhaps the most commonly used example of the serotonin 2A strategy is the combination of an SSRI with trazodone. Clinicians have long recognized that trazodone will improve the agitation and insomnia often associated with SSRIs, allow high doses of the SSRI to be given, and consequently boost the efficacy of the SSRI not only in depression, but also in obsessive-compulsive disorder and other anxiety disorders. Thus, both types of bad math are in play here. 

By the 1990s antidepressants from the serotonin selective reuptake inhibitor (SSRI) class became recognized as preferred first-line treatments for anxiety disorder subtypes, ranging from obsessive-compulsive disorder, to panic disorder, and now to social phobia and posttraumatic stress disorder (Fig. 8—9). Not all antidepressants, however, are afficacious anxiolytics. For example, desipramine and bupropion seem to be of little help in several anxiety disorder subtypes. Documentation of efficacy... 

Dopamine and obsessive-compulsive disorder. Up to 40% of OCD patients do not respond to SSRIs, Thus, at least some OCD patients fail to demonstrate convincing dys-regulation in serotonin function. Therefore, other neurotransmitters may be involved in the pathophysiology of OCD in some patients. 

FIGURE 9—2. Various treatments can be given in combination for obsessive-compulsive disorder (OCD) (i.e., OCD combos). The basis of all combination treatments is a serotonin selective reuptake inhibitor (SSRI) or clomipramine. Added to this basis may be a serotonin 1A partial agonist, a serotonin 2A antagonist, lithium, a benzodiazepine or a sedative-hypnotic, a conventional antipsychotic or an atypical antipsychotic, or behavioral psychotherapy. 

Table 9-5. Profile of serotonin selective reuptake inhibitors (SSRIs) in obsessive-compulsive disorder (OCD)...

Obsessive-compulsive disorder may be linked to abnormalities of the neurotransmitters serotonin and dopamine. The neuroanatomical basis of OCD may be related to dysfunction in the basal ganglia. The hallmark of treatment for OCD is use of SSRIs plus the tricyclic antidepressant clomipramine. Panic disorder is characterized by unexpected panic attacks, possibly linked to abnormalities in the neurotransmitters norepinephrine and GABA, in the sensitivity of benzodiazepine receptors, or even in the regulation of respiration. Drag treatments include SSRIs, several of the newer antidepressants, high-potency benzodiazepines, many tricyclic antidepressants, and MAO inhibitors. 

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