Mirtazapine side effects

Mirtazapine (Remeron) is a newer antidepressant that also blocks 5-HT reuptake, but additionally has antagonistic effects at adrenergic o2, 5-HT2, and 5-HT3 receptors (Stahl 1998). Mirtazapine appears to have indirect agonistic effects on 5-HTlA receptors, which may contribute to its antidepressant effect (Berendsen and Broekkamp 1997). Nefazodone, as well, has SSRI and 5-HT2 antagonist effects. The 5-HT2 antagonist effects of these antidepressants is believed to be responsible for their lower incidence of sexual side effects (Nutt 1997). 

Nortriptyline (Pamelor). A recent study suggested that the tricyclic antidepressant nortriptyline, like bupropion, is effective in the treatment of smoking cessation. Nortriptyline does not have any significant effect on dopamine reuptake activity, but it does increase norepinephrine availability. Like bupropion, nortriptyline may therefore reduce the physical symptoms of nicotine withdrawal. Because nortriptyline carries the danger of lethality in overdose and has the unfavorable side effect profile of the tricyclics, we do not recommend its use for smoking cessation. However, it does raise the question as to whether other newer antidepressants that increase norepinephrine activity (e.g., venlafaxine, mirtazapine, duloxetine) may also prove to be effective treatments for nicotine withdrawal. 

Antidepressants. There are numerous reasons to expect that antidepressants may be helpful in the treatment of AN. First, depressed mood and other symptoms of depression such as anhedonia, decreased energy, poor concentration, and psychomotor retardation are common in cases of starvation from any cause. Second, AN patients and their family members have high rates of comorbid MDD and OCD, illnesses best treated with antidepressant medications. Finally, weight gain is a well-documented side effect of many antidepressants including the tricyclic antidepressants (TCAs) and mirtazapine. 

Medications that enhance norepinephrine activity are used to treat depression and ADHD. Boosting norepinephrine can also produce numerous side effects including nervousness and anxiety, insomnia, and loss of appetite. With mirtazapine and the TCAs, these side effects are usually not a problem because these antidepressants also block histamine receptors. Their antihistamine effects promote increased appetite and drowsiness that tend to offset the side effects that might be experienced from increased norepinephrine activity. 

In cases where the antidepressant response has not been resounding, we prefer switching antidepressants to avoid sexual side effects. The options include bupropion, nefazodone, and mirtazapine, which all effectively treat depression but produce minimal effects on sexual function. Sometimes, if a patient has responded well to one antidepressant but experiences a side effect such as sexual dysfunction, switching within the same class can be a useful approach. 

When we talk about serotonin-blocking medications, a point of clarification must be made. In most cases, medications do not block overall serotonin activity but instead block the activity at one of the many serotonin receptor types. For example, the antidepressants trazodone, nefazodone, and mirtazapine increase total serotonin activity yet they block certain of the serotonin receptors. Mirtazapine increases both serotonin and norepinephrine activity by interfering with the alpha-2 receptor. By also blocking the serotonin-2 and serotonin-3 receptors, mirtazapine avoids the sexual dysfunction and GI side effects commonly experienced with other serotoninboosting medications. We cannot truly call these serotonin-blocking medications, because they are serotonin-boosting medications that selectively block certain serotonin receptors. 

Mirtazapine is indicated for major depression. Its side-effects include sedation and, less commonly, dizziness, abnormal dreams (rarely) and, very rarely, angle-closure glaucoma. 

Pharmacology Tetracyclics enhance central noradrenergic and serotonergic activity. They do not inhibit monoamine oxidase. Although maprotiline and mirtazapine are in the same chemical class, they each affect different neurotransmitters and thus have different side effect profiles. Maprotiline primarily acts by blocking reuptake of norepinephrine at nerve endings. 

Mirtazapine (Panic disorder, PTSD) Few side-effects on initiation few long-term side-effects Relatively safe in overdose Not reported... 

Mirtazapine has a benevolent side-effect profile, and in particular the claims of lower levels of nausea and sexual difficulties appear to be supported by the results of the clinical trials (S. A. Montgomery 1995c). 

Mirtazapine treatment is initiated at a dosage of 15 mg qhs. Depending on clinical response and side effects, the dosage can be increased to a maximum of 45 mg at bedtime, although higher doses are sometimes used in treatment-resistant patients. Elderly patients and individuals with renal or hepatic disease may require lower doses. 

As noted previously, sexual dysfunction and nausea are not commonly associated with mirtazapine treatment. The most common side effects are sedation, weight gain, and dizziness. 

Mirtazapine is associated with modest anticholinergic side effects, including dry mouth and constipation. Anticholinergic side effects and their management are discussed in the Tricyclic and Heterocyclic Antidepressants section later in this chapter. 

TCAs derive their name from their chemical structure aU tricyclics have a three-ring nucleus. Currently, most clinicians are moving away from using TCAs as first-line drugs relative to the newer antidepressants, they tend to have more side effects, to require gradual titration to achieve an adequate antidepressant dose, and to be lethal in overdose. Some data suggest that TCAs may be more effective than SSRIs in the treatment of major depression with melancholic features (Danish University Antidepressant Group 1990 Perry 1996) however, many skilled clinicians and researchers continue to prefer the newer antidepressants, even for patients with melancholia, for the aforementioned reasons. Newer medications that affect both norepinephrine and serotonin (e.g., venlafaxine and mirtazapine) also may have superior efficacy in severely iU depressed patients or when remission is defined as the outcome (Thase et al. 2001). 

Although the efficacy of tricyclic antidepressants in the treatment of unipolar depression is beyond reproach, the side-effect profile of these agents makes them less desirable as first-line therapeutic agents. Introduction of selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine, paroxetine, sertraline, citalopram and fluvoxamine in the past decade has revolutionized the treatment of depression universally. The side-effect profile of SSRIs, such as nausea, diarrhea and sexual dysfunction, is considerably more benign than that of tricyclic drugs. Multiple controlled trials have proven the efficacy of SSRIs vs. placebo (Nemeroff, 1994). Recently, a number of SNRIs (serotonin and noradrenaline reuptake inhibitors) and so-called atypical antidepressants have been marketed that may have additional advantages over SSRIs, such as more rapid onset of action (venlafaxine. mirtazapine) and low sexual side-effect potential ( bupropion, nefazodone). Additionally, it appears that venlafaxine may be more efficacious in cases of treatment-refractory depression (Clerc et al., 1994 Fatemi et al., 1999). Finally, in a recent report (Thase et al., 2001),... 

Treatment of GAD can be undertaken using a number of pharmacological agents. Benzodiazepines have been found to be superior to placebo in several studies and all benzodiazepines appear to be equally effective. However, side effects include sedation, psvchomotor impairment, amnesia and tolerance (Chapter 1). Recent clinical data indicate that SSRIs and SNRIs are effective in the treatment of acute GAD symptoms. Venlafaxine, paroxetine and imipramine have been shown to be effective antianxiety medications in placebo-controlled studies. Case studies also indicate the usefulness of clomipramine, nefazodone, mirtazapine, fluoxetine and fluvoxamine in GAD. Buspirone, a 5-HTla receptor partial agonist, has been shown to be effective in several placebo-controlled, double-blind trials (Roy-Byme and Cowley, 2002). Buspirone has a later onset of action than both benzodiazepines and SSRIs but with the advantage of being non-addictive and non-sedating. 

A number of antidepressants do not fit neatly into the other classes. Among these are bupropion,mirtazapine, amoxapine, and maprotiline (Figure 30-5). Bupropion has a unicyclic aminoketone structure. Its unique structure results in a different side-effect profile than most antidepressants (described below). Bupropion somewhat resembles amphetamine in chemical structure and like the stimulant, has central nervous system (CNS) activating properties. 

Mirtazapine was introduced in 1994 and, like bupropion, is one of the few antidepressants not commonly associated with sexual side effects. It has a tetracyclic chemical structure and belongs to the piperazino-azepine group of compounds. 

Mirtazapine, amoxapine, and maprotiline have tetracyclic structures. Amoxapine is the /V-methylated metabolite of loxapine, an older antipsychotic drug. Amoxapine and maprotiline share structural similarities and side effects comparable to the TCAs. As a result, these tetracyclics are not commonly prescribed in current practice. Their primary use is in MDD that is unresponsive to other agents. 

At present, SSRIs are the most commonly prescribed first-line agents in the treatment of both MDD and anxiety disorders. Their popularity comes from their ease of use, tolerability, and safety in overdose. The starting dose of the SSRIs is usually the same as the therapeutic dose for most patients, and so titration may not be required. In addition, most SSRIs are now generically available and inexpensive. Other agents, including the SNRIs, bupropion, and mirtazapine, are also reasonable first-line agents for the treatment of MDD. Bupropion, mirtazapine, and nefazodone are the antidepressants with the least association with sexual side effects and are often prescribed for this reason. However, bupropion is not thought to be effective in the treatment of the anxiety disorders and may be poorly tolerated in anxious patients. The... 

FIGURE 7—12. When mirtazapine blocks histamine 1 receptors, it can cause anxiolytic actions, but also sedation and weight gain as side effects. 

Mirtazapine [Remeron] Exact mechanism unclear may increase norepinephrine and serotonin activity by blocking inhibitory presynaptic autoreceptors Low incidence of sedative, anticholinergic, and cardiovascular side effects May cause agitation, anxiety, other mood changes... 

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