Side effects of SSRIs

SSRIs are the drugs of choice for PD. All SSRIs have demonstrated effectiveness in controlled trials, with 60% to 80% of patients achieving a panic-free state.28,48,49 With similar efficacy reported and no trials comparing SSRIs with other SSRIs, selection generally is based on pharmacokinetics, drug interactions, side effects, and cost differences (see Chap. 35 for more discussion). The most common side effects of SSRIs include headaches, irritability, nausea and other gastrointestinal complaints, insomnia, sexual dysfunction, increased anxiety, drowsiness, and tremor.49 SSRIs should not be discontinued abruptly to avoid a withdrawal syndrome characterized by dysphoric mood, irritability, and agitation. 

The initial dose of SSRI is similar to that used in depression. Patients should be titrated as tolerated to response. Many patients will require maximum recommended daily doses. Patients with comorbid panic disorder should be started on lower doses (Table 37-4). When discontinuing SSRIs, the dose should be tapered slowly to avoid withdrawal symptoms, with the possible exception of fluoxetine. Relapse rates may be as high as 50%, and patients should be monitored closely for several weeks.58 Side effects of SSRIs in SAD patients are similar to those seen in depression and most commonly include nausea, sexual dysfunction, somnolence, and sweating. 

Since the introduction of the first approved SSRI, fluoxetine (1) in 1987 [9], a number of SSRIs have been developed for the treatment of depression [2], Currently, the five most commonly prescribed SSRIs are fluoxetine, escitalopram (2, S-enantiomer of citalopram), sertraline (3), paroxetine (4) and fluvoxamine (5). Recent effort in the clinical development of new SSRIs has focused on the treatment of premature ejaculation (PE) by taking advantage of the ejaculation-delaying side effects of SSRIs [10]. Although SSRIs have been prescribed off-label to treat this condition, an SSRI with rapid onset of action and rapid clearance could be preferred for on-demand treatment of PE [11,12]. Dapoxetine (LY210448, 6), an... 

The most common adverse side effects of SSRI medications, in decreasing order, include sexual dysfunction (30%), nausea, drowsiness, constipation, nervousness, and fatigue (>10%) (Preskorn, 2000). Nervousness includes anxiety, agitation, hostility, akathisia, and cen-... 

Mild nausea, loose bowel movements, anxiety, headache, insomnia, and increased sweating are frequent initial side effects of SSRIs. They are usually dose related and may be minimized with low initial dosing and gradual titration. These early adverse effects almost always attenuate after the first few weeks of treatment. Sexual dysfunction (see Sexual Dysfunction subsection later in this section) is the most common long-term side effect of SSRIs. 

Decreased libido, anorgasmia, and delayed ejaculation are common side effects of SSRIs. When possible, management of sexual side effects should be postponed until the patient has completed an adequate trial of the antidepressant. 

Table 1.7 The most common side effects of SSRIs, SNRIs and other newer antidepressants (Sadock and Sadock, 2001)...

C. Serotonin pathways and receptors that mediate therapeutic actions and side effects of SSRIs... 

Serotonin Pathways and Receptors That Mediate Therapeutic Actions and Side Effects of SSRIs... 

FIGURE 6-39. Mechanism of action of serotonin selective reuptake inhibitors (SSRIs)—part 5. Finally, once the SSRIs have blocked the reuptake pump (Fig. 6-36), increased somatodendritic serotonin (Fig. 6-36), desensitized somatodendritic serotonin 1A autoreceptors (Fig. 6—37), turned on neuronal impulse flow (Fig. 6-38), and increased release of serotonin from axon terminals (Fig. 6— 38), the final step shown here may be the desensitization of postsynaptic serotonin receptors. This has also been shown in previous figures demonstrating the actions of monoamine oxidase (MAO) inhibitors (Fig. 6-4) and the actions of tricyclic antidepressants (Fig. 6—6). This desensitization may mediate the reduction of side effects of SSRIs as tolerance develops. 

PROTEASE INHIBITORS SSRIs t adverse effects of fluoxetine, paroxetine and sertraline when co-administered with ritonavir (with or without lopinavir). Cardiac and neurological events have been reported, including serotonin syndrome Ritonavir is associated with the most significant interaction of the protease inhibitors due to potent inhibition of CYP3A, CYP2D6, CYP2C9 and CYP2C19 isoenzymes Warn patients to watch for t side-effects of SSRIs and consider 1 dose ofSSRI... 

Clomipramine, fluvoxamine, sertraline, and fluoxetine are approved by the FDA for treatment of OCD in children and adolescents. Childhood and adult OCD appear to respond similarly to drug therapy. The SSRIs appear to be effective and well tolerated in treatment of OCD in children and are generally considered first-line agents. Treatment with an SSRI produces a favorable response in 75% of children and adolescents with OCD. A combination of SSRIs and CBT is preferred in most cases. In children, the most commonly described side effects of SSRI therapy include nausea, headache, tremor, gastrointestinal complaints, drowsiness, akathisia, insomnia, disinhibition, and agitation. Clomipramine was significantly better than placebo in the treatment of OCD in children and adolescents, with 75% of patients having a moderate to marked improvement. Clomipramine was also more effective than desipramine in children and adolescents. ... 

---