Gastrointestinal SSRIs

FIGURE 47.1 Suggested algorithm for the use of psychotropic medications in the medically ill child or adolescent. CNS, central nervous system GI, gastrointestinal SSRI, selective serotonin reuptake inhibitor TLA, tricyclic antidepressant. 

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 reason for this warning is that abrupt cessation of SSRIs produces withdrawal symptoms in about 20 per cent of patients. Symptoms of withdrawal from antidepressant medication include gastrointestinal disturbances (abdominal cramping and pain, diarrhoea, nausea and vomiting), flu-like symptoms, headaches, sleep disturbances, dizziness, blurred vision, numbness, electric-shock sensations, twitches and tremors. Abrupt withdrawal can also produce symptoms of depression and anxiety, which can occur within hours of the first missed dose of the drug.11 Withdrawal symptoms are sometimes mistaken for a relapse, leading patients to resume antidepressant medication and to conclude that they need it in order to remain free of depression. Technically, this is not considered addiction , but it does seem awfully close. 

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. 

Selective serotonin re-uptake inhibitors (SSRIs) and tricyclic antidepressants are equally effective. Hov/ever, SSRIs tend to have fewer antimuscarinic side-effects and are less cardiotoxic in case of overdosage. SSRIs tend to cause gastrointestinal side-effects. Both SSRIs and tricylic antidepressants exhibit a time lag before the action of the antidepressants becomes effective. 

Citalopram is a selective serotonin re-uptoke inhibitor (SSRI). These tend to have fewer ontimuscarinic effects than tricyclic antidepressant (TCA) drugs, such as dry mouth and constipation however, SSRIs tend to cause gastrointestinal effects, such as nausea and vomiting. MAOIs are monoamine oxidase inhibitors. 

Nausea is a common early side effect of all SSRIs. Early nausea is probably attributable to the stimulation of serotonin type 3 (5-HT3) receptors in the gastrointestinal tract, which downregulate after several weeks of treatment. Hence this side effect is both dose dependent and transient. Some patients report less nausea if they take the medication with food. Although rarely needed, medication that blocks the 5-HT3 receptor (e.g., ondansetron) can be used to reduce SSRI-induced nausea. 

The side-effect profile of venlafaxine is similar to that of SSRIs and includes gastrointestinal symptoms, sexual dysfunction, and transient discontinuation symptoms. Like the SSRIs, venlafaxine does not affect cardiac conduction or lower the seizure threshold. In most patients, venlafaxine is not associated with sedation or weight gain. Side effects that differ from those of SSRIs are hypothesized to be related to the increased noradrenergic activity of this drug at higher doses these side effects are dose-dependent anxiety (in some patients) and dose-dependent hypertension. 

The SSRIs, venlafaxine, or nefazodone may be reasonable alternatives to earlier generation antidepressants because of their less problematic side effect profiles (486). The propensity to increase activity, the lack of sedation, gastrointestinal symptoms, and alterations in blood pressure are potential complications, however. Given AIDS-induced altered metabolism, for many of these agents, TDM may be helpful in establishing an effective, nontoxic dose. 

The adverse effects of the most commonly prescribed antidepressants—the SSRIs—can be predicted from their potent inhibition of SERT. SSRIs enhance serotonergic tone, not just in the brain but throughout the body. Increased serotonergic activity in the gut is commonly associated with nausea, gastrointestinal upset, diarrhea, and other gastrointestinal... 

Sedative effects, particularly with trazodone, can be quite pronounced. Thus, it is not surprising that the treatment of insomnia is currently the primary application of trazodone. The gastrointestinal effects appear to be dose-related and are less pronounced than those seen with SNRIs or SSRIs. Sexual effects are uncommon with nefazodone or trazodone treatment as a result of the relatively selective serotonergic effects of these drugs on the 5-HT2 receptor rather than on... 

Antidepressants do not appear to elevate mood in healthy volunteers (see Chapter 10), but neither, as we have seen, is there good evidence that they do so in depressed patients. Although reports of effects of SSRIs suggest that effects on sleep may sometimes differ between patients and volunteers (Mayers Baldwin 2005), in general side effects of antidepressants in patient trials are consistent with those found in healthy volunteers. For example, tricyclics show sedation and cognitive impairment (Deptula Pomara 1990 Herrmann McDonald 1978), while SSRIs show gastrointestinal upset and drowsiness in both patients and volunteers (Dumont et al. 2005). 

A Norwegian study by Olav Spigset utilizing that country s Adverse Drug Reactions Monitor Center reviewed 1,202 reports describing 1,861 adverse reactions to SSRIs. Again, the pattern of reports for the individual SSRIs (citalopram, fluoxetine, fluvoxamine, paroxetine, and sertraline) was very similar, with three exceptions. Fluvoxamine reports were comparatively elevated for gastrointestinal symptoms, fluoxetine... 

Prozac and the other SSRIs, as well as any antidepressant that blocks the removal of serotonin from the synapse, can produce a well-documented, severe condition called the serotonin syndrome (Sternbach, 1991). This disorder includes the usual signs of overstimulation, such as euphoria and hypomania, agitation, confusion, and gastrointestinal upset, including diarrhea. However, the serotonin syndrome additionally involves overstimulation of the brain stem and spinal cord, producing fever and chills, severe incoordination, muscle spasms, and hyperactive reflexes. It bears some similarity to neuroleptic malignant syndrome, and like NMS it can also be lethal (chapter 4). 

Q13 Patients who take SSRIs might develop gastrointestinal disturbances such as dyspepsia, nausea and vomiting, weight gain, headaches because of the vasodilator effects of serotonin in some patients insomnia may occur. 

The major advantages of SSRIs over the tricyclic antidepressants are their less pronounced anticholinergic adverse effects and lack of severe cardiotoxicity. However, some studies have shown some degree of nervousness or agitation, sleep disturbances, gastrointestinal symptoms, and perhaps sexual adverse effects more commonly in patients treated with SSRIs than in those treated with tricyclic antidepressants. SSRIs may also be associated with an increased risk of suicide, particularly in children under 16 (9). 

There seems to be little difference between SSRIs with respect to frequency and severity of adverse effects. The most common adverse effects are gastrointestinal disturbances (nausea, diarrhea/loose stools, constipation incidence 6-37%), nervous system effects (insomnia, somnolence, tremor, dizziness and headache 11-26%), and effects on the autonomic nervous system (dryness of the mouth and sweating 9-30%) (2,10). Weight gain or weight loss have been documented relatively infrequently (2). A high frequency of sexual disturbances has been... 

Gastrointestinal adverse effects are one of the major disadvantages of SSRIs. The most common is nausea, and the incidence is said to be 20% or more for paroxetine (45,46), sertraline (47), fluvoxamine (5), fluoxetine (48), and citalopram (10,49). Although nausea can lead to drug withdrawal, it usually disappears after a few weeks. Other gastrointestinal symptoms that occur commonly with fluoxetine and sertraline are loose stools and diarrhea (47,48,50), while constipation has been more often reported with fluvoxamine (5) and paroxetine (45,46). 

Gastrointestinal adverse effects are one of the major disadvantages of SSRIs. The most common is nausea, and the incidence is said to be 20% or more for citalopram (19,20). 

Adding mirtazapine s 5FIT3 antagonism to venlafaxine or SSRIs may reverse drug-induced nausea, diarrhea, stomach cramps, and gastrointestinal side effects... 

Often a preferred treatment of anxious depression as well as major depressive disorder comorbid with anxiety disorders Withdrawal effects may be more likely than for some other SSRIs when discontinued (especially akathisia, restlessness, gastrointestinal symptoms, dizziness, tingling, dysesthesias, nausea, stomach cramps, restlessness)... 

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