Anxiety disorders mirtazapine

Mirtazapine (Remeron). Mirtazapine is the newest of the atypical antidepressants. It mainly works by blocking the alpha-2 negative feedback receptor and thus increases norepinephrine and serotonin activity. In addition, mirtazapine blocks serotonin-2 and serotonin-3 receptors to produce a specific serotonin action like nefazodone. Mirtazapine is approved for the treatment of depression. Its use in the anxiety disorders is being studied. 

Serotonin-Boosting Antidepressants. The SSRIs have also been studied in the treatment of generalized social anxiety disorder, and paroxetine, sertraline, and venlafaxine are effective. Preliminary data suggests that the serotonin-boosting atypical antidepressants (mirtazapine and nefazodone) may also be helpful. Like the MAOIs, they appear to be effective at doses comparable to those used to treat depression. They may help avoidant patients to gradually increase their social interaction and become more assertive. 

Antidepressants. The most widely used psychiatric medicines with the broadest range of application in TBI patients are undoubtedly the SSRI antidepressants. They are well tolerated, unlikely to worsen any of the preexisting deficits associated with TBI, and offer relief from not only depression but also impulsivity and virtually all variants of anxiety in these patients. As such, SSRIs are the preferred first-line treatment for all anxiety disorders after TBI. Other newer antidepressants that also work (at least in part) by boosting serotonin activity, namely, mirtazapine (Remeron), nefazodone (Serzone), venlafaxine (Effexor XR), and duloxetine (Cymbalta) can also be considered, but they have not been well studied in patients with TBI. In... 

Taken together, the efficacy of antidepressants covers the spectrum of anxiety disorders, although there are important differences between drugs in the group (Table 3). Several new antidepressants have been marketed since the SS-RIs venlafaxine and mirtazapine are discussed later (Sects. 3.2.1.2 and 3.2.1.4) nefazodone, a serotonin reuptake inhibitor and postsynaptic 5-HT2 blocker showed promise in early studies but was recently withdrawn by its manufacturers reboxetine, a noradrenaline reuptake inhibitor (NARI) showed benefits in panic disorder in one published study (Versiani et al. 2002) and further evidence of its anxiolytic efficacy is awaited. 

Mirtazapine has a novel mechanism of action that in theory should promote anxiolytic effects, although evidence from studies of anxiety disorders is awaited. It increases synaptic release of serotonin and noradrenaline via blockade of presynaptic inhibitory a2-adrenoceptors, as well as blocking post-synaptic 5-HT2 and 5-HT3 serotonin receptors and Hi histamine receptors. Mirtazapine has good efficacy for anxiety symptoms associated with depression (Fawcett and Barkin 1998), and in controlled studies was superior to... 

Enkelmann R (1991) Alprazolam versus buspirone in the treatment of outpatients with generalized anxiety disorder. Psychopharmacology (Berl) 105 428-432 Faravelli C, Rosi S, Truglia E (2003) Treatments benzodiazepines. In Nutt DJ, BaUenger JC (eds) Anxiety disorders. Blackwell Science, Oxford, pp 315-338 Fawcett J, Barkin RL (1998) A meta-analysis of eight randomized, double-blind, controlled clinical trials of mirtazapine for the treatment of patients with major depression and symptoms of anxiety. J Clin Psychiatry 59 123-127 Febbraro GA, Clum GA (1998) Meta-analytic investigation of the effectiveness of self-regulatory components in the treatment of adult problem behaviors. Clin Psychol Rev 18 143-161... 

The other tertiary TCA that has dual serotonergic-noradrenergic effects, amitriptyline, like imipramine, appears to be consistently effective in anxiety disorders. Newer antidepressants such as mirtazapine, nefazodone, paroxetine, and venlafaxine may also benefit patients with anxiety disorder ( 60, 61, 62 and 63). 

Goodnick PJ, Puig A, DeVane CL, et al. Mirtazapine in major depression with comorbid generalized anxiety disorder. J Clin Psychiatry 1999 60 446-448. 

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... 

In addition to its efficacy as a first-line antidepressant, mirtazapine may have enhanced efficacy due to its dual mechanism of action (Fig. 7—3), especially in combination with other antidepressants that block serotonin and/or norepinephrine reuptake. This will be discussed below in the section on antidepressant combinations. Mirtazapine may also have utility in panic disorder, generalized anxiety disorder, and other anxiety disorders, but has not been intensively studied for these indications. 

Novel antidepressants Given the importance of SSRIs in the treatment of panic disorder, other, newer antidepressants are developing an efficacy portfolio for panic disorder (and other anxiety disorders) as well. Thus, venlafaxine XR, nefazodone, and mirtazapine hold promise for the treatment of panic disorder. One early study also suggests that the new antidepressant reboxetine may be effective in panic disorder. 

HT2 antagonists appear to have efficacy in GAD but not panic disorder (which then may exacerbate). No 5-HT2 antagonists are marketed for anxiety disorders but antidepressants with 5-HT2 antagonism include trazodone, mirtazapine and nefazodone. 

Ostacher MJ, Eisner L, Nierenberg AA. Mirtazapine in the treatment of mood and anxiety disorders. Expert Rev Neurotherap 2003 3 425 33. 

A 10-year-old boy with ADHD, oppositional defiant disorder, and generalized and separation anxiety disorders started taking OROS methylphenidate 18 mg/day and fluoxetine 10 mg/day. Four days later, he had an acute episode of intense hallucinations 3 hours after taking the medications. His mother reported that the visual hallucinations lasted about 1 hour and the tactile hallucinations more than 2 hours. Two days later he had a similar episode. His mother withdrew the medications for 10 days, during which time he was symptom free. When OROS methylphenidate 18 mg/day monotherapy was restarted he did not report any hallucinations. Mirtazapine 15 mg/day was added for symptoms of anxiety and sleep disturbances. During the next 2 months his condition improved and he had no further hallucinations. 

Mirtazapine is an antidepressant with a novel mechanism of action affecting both 5-HT and noradrenergic function. A recent systematic, open-label study found that 9 (34.6%) of 26 subjects (5 females, 21 males mean age, 10.1 +/— 4.8 years, age range 3.8-23.5 years) with autistic disorder and other PDDs were much improved or very much improved on the CGI after a mean duration of treatment of 5 months (Posey et al., 2001). The dosage range for mirtazapine was 7.5 to 45 mg/day with a mean daily dose of 30.29 mg +/— 12.64 mg. Target symptoms of aggression, self-injury, irritability, hyperactivity, anxiety, depression, and insomnia showed improvement. Adverse effects were transient and minimal and included increased appetite, irritability, and sedation. Based upon these preliminary data, a double-blind, placebo-controlled trial appears warranted. 

For MDD with severe anxiety, mirtazapine, TCAs, trazodone, and benzodiazepines should be considered as adjunctive therapy. If the patient is not at least moderately improved after 4-8 weeks, the treatment regimen should be reappraised. Compliance should be checked. It is important to consider pharmacokinetic/pharmacodynamic factors (this may require an evaluation of serum levels of the antidepressant medication), general medical comorbidities, and comorbid psychiatric disorders, including substance abuse and significant psychosocial problems. The initial therapeutic treatment dose should be gradually maximized. For partial responders, the trial should be extended by... 

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