A SSRIs

MAOI non-selective monoamine oxidase (A/B) inhibitors RIMA reversible inhibitor of monamine oxidase type A SSRI selective serotonin (5-HT) reuptake inhibitors SNRI serotonin/noradrenaline reuptake inhibitor SNARI selective noradrenaline (NA) reuptake inhibitor NA = 5-HT — DA potency of the drug is very similar in raising the level of both (or all three) monamines NA > 5-HT more selective for NA 5-HT>NA more selective for 5-HT NA increases the release of NA. 

When starting a SSRI, the abrupt increase in serotonin may cause side effects. In the brain, the short-term effects include headache, sleep disturbance, nervousness, anxiety, and tremulousness. The digestive system effects include nausea, loose stools, decreased appetite, and indigestion. Most of these effects are mild and shortlived or can be managed with over-the-counter remedies. Nausea, for example, can be minimized by taking a SSRI after meals. These effects are also commonly seen with venlafaxine and duloxetine, atypical antidepressants that block serotonin reuptake like the SSRIs. 

The first-line medication for the treatment of BN will usually be a SSRI of which fluoxetine is the best studied. Aimough most antidepressants effectively treat BN at doses comparable to mose routinely used to treat depression, fluoxetine is considerably more effective at 60mg/day than lower doses. 

Serotonin-Boosting Antidepressants. Antidepressants that enhance serotonin activity in the brain have also been studied in ADHD. In particular, fluoxetine (Prozac) and the serotonin-selective TCA clomipramine (Anafranil) have been the most extensively evaluated, with mixed success. They provide some benefit for aggression and impulsivity but don t significantly improve the poor attention of ADHD. As a result, the SSRls and other serotonin-boosting antidepressants do not appear to be effective first-line treatments for ADHD. Conversely, depressed patients without ADHD often show improvements in symptoms of concentration and attention when treated with a SSRI. Although SSRls are not widely used in the treatment of ADHD, they may be worthy of consideration in ADHD patients whose impulsivity is not controlled by stimulants alone. Those with comorbid conduct disorder or ODD who are prone to agitation and at times violent outbursts may be helped by the addition of a SSRI. 

Among these choices, bnspirone is preferred if the patient is also experiencing anxiety. If the patient is depressed and agitated, a SSRI should be tried first. Second line choices inclnde carbamazepine (Tegretol) or one of the atypical antipsychot-ics—ziprasidone (Geodon), risperidone (Risperdal), olanzapine (Zyprexa), quetiap-ine (Seroquel), or aripiprazole (Abilify) can be tried. If psychotic symptoms are present, one of the atypical antipsychotics should be tried first. 

Be Patient. Probably the simplest way to manage a side effect is just to wait it out. Granted, this is easier said than done, but sometimes, a side effect that occurs upon starting a new medication resolves within a few days. For example, this is typically the case with the gastrointestinal side effects often experienced by patients prescribed serotonin renptake inhibitors. Within a few days, a patient beginning a SSRI will become adjnsted to the increased levels of serotonin and the stomach queasiness resolves. We find that when advising patients of potential side effects, it helps to reassnre them that certain side effects will likely be short-lived. 

Treatment of choice - second-generation antidepressants such as a SSRI,... 

In general, the SSRIs have a more tolerable side effect profile than the tricyclic antidepressants with their anticholinergic effects. Review of the rate that subjects in the controlled studies discontinued a SSRI because of adverse effects provides some perspective on how well tolerated the medications are, although the specifics may vary according to dosage and design (e.g., forced titration) and are not directly comparable. The rate of discontinuation was reported to be 12% (4/48) for fluoxetine (Emslie et ah, 1997), 9.7% for paroxetine (Keller et ah, 2001), 13% (12/92) for sertraline (March et ah, 1998), and 33% (19/57) (Riddle et ah, 2001) and 7.9% (5/63) for fluvoxamine (Walkup et ah, 2001). 

Much of the time, treatment-extant literature doesn t provide much guidance when the patient has multiple comorbidities or already has failed best-practice initial interventions. The few available comparative treatment trials that include both medication and psychotherapy all focus on acute treatment or, less commonly, the heroic management of treatment-refractory patients. This leaves out the majority of patients for whom combined treatment is appropriate if not de rigueur, namely those who are partial responders to initial treatment and/or who require a combination of treatments because of comorbidity. Furthermore, for many clinically important decisions, it is unlikely that there will ever be randomized evidence. For example, how many SSRI trials should precede a clomipramine trial in the partially responsive child with OCD Flow long does one wait before adding a SSRI when treating a child with OCD who is not particularly responsive to weekly CBT ... 

For patients who do not respond to a specific antidepressant medication or who do not tolerate its side effects, other antidepressants of the same class or different classes (e.g., venlafaxine for a patient treated with a SSRI) can be tried. The few adult studies published thus far suggest that it is more efficacious to switch antidepressant classes than to stay within the same class, because of the probable heterogeneity in underlying depression mechanisms. Also, it has been suggested that severe depressions appear to respond better to antidepressants with both serotonergic and adrenergic properties (e.g., venlafaxine) (Poirier and Boyer, 1999). 

Case reports have suggested that adding stimulant medications or combining a SSRI and a TCA or bupropion may also be effective (APA, 2000), but these combinations need to be done with caution, given the possibility of drug interactions (e.g., SSRIs cytochrome inhibition leading to toxic TCA levels). Additionally, in adults, the combination of antidepressants and psychotherapy (CBT, IPT) for patients with severe or treatment-resistant depression has been found useful (APA, 2000 Keller et al., 2000). 

Eor example, depressed adolescents with comorbid ADHD respond less well to treatment (Emslie et al., 1998 Hamilton and Bridge, 1999 Birmaher et al., 2000b). For these patients, it has been suggested that the ADHD be initially treated and if depressive symptoms persist after stabilization of the ADHD, a SSRI... 

A more common approach in difficult to treat cases would be the combination of clomipramine with a SSRI several reports lend support to this practice (Simeon and Thatte, 1990 Figueroa et al., 1998). In this situation, careful attention to the potential pharmacokinetic interactions discussed above are recommended. Sertraline and citalopram are least likely to elevate tricyclic levels due to less potential GYP interactions. By expert consensus, second- (venlafaxine) and third-line (nefazadone and gabapentin) agents may be used when clinical response is inadequate despite a lack of controlled data. Venlafaxine may be substituted for a more typical SSRI while nefazadone or gabapentin may be added to either clomipramine or a SSRI. The combination of venlafaxine with other SSRIs is not generally recommended as it may increase the risk of a serotonin syndrome. The addition of nefazadone to SSRIs presents a lesser risk. 

Studies of the use of the specific serotonin-uptake inhibitors (SSRIs) to treat OCD suggest that, compared to non-tic-related OCD, tic-related OCD is less responsive to SSRI monotherapy (McDougle et al., 1993, 1994). Addition of a neuroleptic, such as haloperidol (McDougle et ah, 1994), risperidone (McDougle et al., 2000), or olanzapine (Bogetto et al., 2000), appears to be useful in improving treatment-resistant individuals response to a SSRI. It is unclear whether this pattern of treatment response is specifically associated with a comorbid tic disorder the pattern of obsessive compulsive symptoms characteristic of TS or yet some other predictors. 

In a retrospective case analysis, fluoxetine (20 to 80 mg daily) and paroxetine (20 to 40 mg daily) were found to be effective in approximately one-quarter of adults (mean age, 39 years) with intellectual disability and autistic traits (Branford et al., 1998). The sample consisted of all intellectually disabled subjects who had been treated with a SSRI over a 5-year period within a health-care service in Great Britain. The mean duration of treatment was 13 months. Target symptoms were perseverative behaviors, aggression, and self-injurious behavior. Six of 25 subjects treated with fluoxetine and 3 of 12 subjects given paroxetine were rated as much improved or very much improved on the CGI. 

Citalopram. To date, there have been no published reports on the effects of citalopram, a SSRI which has been recently introduced in the United States, in patients with autistic disorder or other PDDs. 

In the antipressant group, 92.1% were treated with a SSRI, most commonly citalopram (47.9%) or sertraline (29.3%). The indications for prescribing antidepressants were depression in 59.2%, OCD in 29.8%, anxiety disorder in 10.7%, and eating disorder in 6.3% of those treated with an antidepressant (Sorensen et al. 2002, in press). Of the total population of 0 to 8-year-... 

Useful alternative to stimulants in ADHD, but exacerbation of tics has been reported Under 150 mg/day, similar to a SSRI Noradrenergic effects at higher doses... 

Note. L=liquid CR=controlled release SR=sustained-release XR=extended-release soltab=orally disintegrating tablets MAOI=monoamine oxidase inhibitor MAO A=monoamine oxidase A SSRI=selective serotonin reuptake inhibitor SNRI=sCTotonin-norepinephrine reuptake inhibitor. 

Few data are available to guide this decision beyond clinical experience. There is a modest amount of evidence that nonresponders to TCAs, principally desipramine or imipramine, alone may respond to a SSRI alone and vice versa (136). No compelling evidence exists showing that nonresponders to one SSRI as a result of a lack of efficacy will respond to a second trial with another SSRI. There is limited confidence in the results of studies that have been done switching nonresponders from one SSRI to another for two reasons. First, virtually all have been open label and, second, most were conducted by the manufacturer of the second SSRI. Until there is more substantive evidence that switching from one SSRI to another is worthwhile, it may be more prudent to switch to a class of antidepressants with a different putative mechanism of action. 

Diler RS, Avci A. SSRI-induced mania in obsessive-compulsive disorder. J Am Acad Child Adolesc Psychiatry 1999 38(1) 6—7. 

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