Anxiety from SSRIs

Generalized Sociai Anxiety Disorder, Treatment Resistance. A significant minority of patients will not experience a satisfactory treatment response to antidepressant therapy, even after a trial of adequate duration at full strength doses. For those with comorbid depression who are experiencing no benefit from SSRI treatment for either the anxiety or depression, then switching treatment is advisable. The options include switching to another SSRI, a SNRI (venlafaxine or perhaps dulox-etine), or, when other alternatives fail, phenelzine. 

In recent years many of these primary care cases that would formerly have been seen as anxiety disorders have been portrayed as anxious-depressives and have led to treatment with antidepressants, in particular the more recent serotonin reuptake inhibitors. As part of this rebranding a variety of states such as panic disorder, post-traumatic stress disorder, social phobia and generalized anxiety disorder have appeared, along with more traditional disorders such as obsessive compulsive disorder (OCD). Many of these diagnoses are likely to lead to prescriptions of an SSRI although the evidence for benefit from SSRIs is poor except for OCD. 

Tone, Andrea. The Age of Anxiety A History of America s Turbulent Affair with Tranquilizers. New York Basic Books, 2009. This book traces the history of drugs to treat anxiety from the first tranquilizer sold in 1955 to the billions of antianxiety drugs sold today. Although tranquilizers like Valium fell out of favor because of their addictiveness, the use of selective serotonin reuptake inhibitor (SSRI) antidepressants have become widely popular treatments for anxiety. The book places the popularity of these types of drugs within the larger context of what Tone calls the tranquilizer culture. 

FIGURE 69-3. Algorithm for the pharmacotherapy of social anxiety disorder. SSRI = selective serotonin reuptake inhibitor, BZ = benzodiazepine. (Compiled from Ballenger et al, Van Amerigen and Mancini, and Blanco... 

Antidepressant drugs are used to manage depressive episodes such as major depression or depression accompanied by anxiety. These drugs may be used in conjunction with psychotherapy in severe depression. The SSRIs also are used to treat obsessive-compulsive disorders. The uses of individual antidepressants are given in the Summary Drug Table Antidepressants. Treatment is usually continued for 9 months after recovery from the first major depressive episode. If the patient, at a later date, experiences another major depressive episode, treatment is continued for 5 years, and with a third episode, treatment is continued indefinitely. 

SSRIs are theorized to reduce the frequency of hot flashes by increasing serotonin in the central nervous system and by decreasing LH. Of the SSRIs, citalopram, paroxetine, and sertraline all have been studied and have demonstrated a reduction in hot flashes while treating other symptomatic complaints such as depression and anxiety.33 Venlafaxine, which blocks the reuptake of serotonin and norepinephrine, has demonstrated a reduction in hot flashes primarily in the oncology population.34 Overall, these antidepressant medications offer a reasonable option for women who are unwilling or cannot take hormonal therapies, particularly those who suffer from depression or anxiety. These agents should be prescribed at the lowest effective dose to treat symptoms and may be titrated based on individual response. 

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. 

Fluvoxamine (Luvox). This is actually the oldest of the SSRIs. It is approved iu this couutry for the treatmeut of OCD but is also an effective treatment for major depression and many other anxiety disorders. It should be started at 50mg/day, and the effective dose range is from 100 to 300mg/day. Fluvoxamine is the only SSRI that must be takeu twice a day. The common side effects of fluvoxamine are comparable to other SSRIs. 

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... 

Kessler RC (2001) Comorbidity of depression and anxiety disorders. In Montgomery SA, den Boer JA (eds) SSRIs in depression and anxiety. Wiley, Chichester, pp 87-106 Kessler RC, Price RH (1993) Primary prevention of secondary disorders a proposal and agenda. Am J Community Psychol 21 607-633 Kessler RC, McGonagle KA, Zhao S (1994) Lifetime and 12-month prevalence of DSM-III-R psychiatric disorders in the United States. Results from the National Comorbidity Survey. Arch Gen Psychiatry 51 (1) 8-19... 

The current state on the pharmacotherapy of anxiety disorders is summarized by J.R. Nash and D.J. Nutt. The recent shift in clinical practice towards the use of antidepressants, particularly SSRIs, for the first-fine treatment of anxiety disorders is supported by research evidence from randomized controlled trials. It is only in recent years that drugs acting via GABA neurotransmission have been supplanted as first-line treatments, and new drugs in this class with improved tolerability compared to the benzodiazepines are likely to be marketed in the near future. 

The low side effect profile, ease of use, and powerful clinical effect of the selective serotonin reuptake inhibitors (SSRIs) revolutionized the treatment of depression and anxiety in the 1990s. The success of the SSRIs shifted the focus from noradrenergic to serotonergic mechanisms in these common disorders. 

If there is a relationship between depression and anxiety, it is not surprising that certain drugs work to treat both. Ample evidence from both humans and animals suggests that the serotonergic system is altered in both types of disorders, and SSRI use is effective in the treatment of both disorders. It should be noted, however, that people who exhibit both disorders tend to be sicker for longer than those with only one disorder, and patients who have comorbid anxiety and depression do not respond as well to SSRI treatments. 

There are several SSRIs currently being prescribed for the treatment of anxiety. Compared to the benzodiazepines and other classes of antidepressants, they are safer, causing milder side effects and fewer problems with overdose. Because they affect serotonin systems, which also play a large role in sleep patterns, the SSRIs can have effects on sleep, which vary from patient to patient. Generally, these involve a disruption of sleep patterns, but SSRIs can also cause drowsiness. All of the SSRIs are broken down in the liver. 

Although the SSRIs are very similar in action, they differ in several ways, including how tightly they bind to particular receptors on brain cells, which receptors they bind to, how quickly they work, and how quickly they are cleared from the body. For this reason, when one of these medications is not effective in treating an anxiety disorder, others will sometimes be tried and prove effective. 

The commonly used classes of antidepressants are discussed in the following sections, and information about doses and half-lives is summarized in Table 2-1. The antidepressant classes are based on similarity of receptor effects and side effects. All are effective against depression when administered in therapeutic doses. The choice of antidepressant medication is based on the patient s psychiatric symptoms, his or her history of treatment response, family members history of response, medication side-effect profiles, and comorbid disorders (Tables 2-2 and 2-3). In general, SSRIs and the other newer antidepressants are better tolerated and safer than TCAs and MAOIs, although many patients benefit from treatment with these older drugs. In the following sections, clinically relevant information is presented for the antidepressant medication classes individually, and the pharmacological treatment of depression is also discussed. The use of antidepressants to treat anxiety disorders is addressed in Chapter 3. 

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. 

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