Anxiety from antidepressants

Antidepressants differ from benzodiazepines in the onset and course of their actions (Fig. 2). Most cause an increase in anxiety on initiation of therapy, and anxiolytic effects occur later. In comparative studies, improvement matches that on benzodiazepines after 4 weeks (Rocca et al. 1997). Withdrawal effects, particularly rebound, are less problematic with antidepressants, although stopping treatment is associated with a significant rate of relapse, and a withdrawal syndrome has been described for most of the shorter-acting drugs. 

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. 

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. 

Medications that have been used as treatment for anxiety and depression in the postwithdrawal state include antidepressants, benzodia2epines and other anxiolytics, antipsychotics, and lithium. In general, the indications for use of these medications in alcoholic patients are similar to those for use in nonalcoholic patients with psychiatric illness. However, following careful differential diagnosis, the choice of medications should take into account the increased potential for adverse effects when the medications are prescribed to alcoholic patients. For example, adverse effects can result from pharmacodynamic interactions with medical disorders commonly present in alcoholic patients, as well as from pharmacokinetic interactions with medications prescribed to treat these disorders (Sullivan and O Connor 2004). 

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. 

Ultrasonic vocalizations are emitted by rat pups (under the age of 14 days) when they are isolated from their mother, and are thought to reflect anxiety. This measure has proven sensitive to both anxiolytic and anxiogenic manipulation of GABA neurotransmission. However, the early developmental window used is problematic, in that chronic drug administration probably results in a variety of compensatory changes not seen in adulthood, and may alter development of relevant brain systems. Indeed, in contrast to the clinical situation, the antidepressant clomipramine has acute, but not chronic, anxiolytic efficacy in this model. 

Nicotine is responsible for the highly addictive properties of tobacco products. Addiction occurs in 30% of those who experiment with tobacco products, and more than 80% of those who attempt to quit smoking will relapse within a year. Withdrawal from nicotine produces a syndrome characterized by nicotine craving as well as dysphoria, anxiety, irritability, restlessness and increased appetite. It is treated with nicotine replacement therapies, such as nicotine gum and patches, and/or with buproprion, a drug that is classified as an antidepressant but has multiple and complex effects in brain. Buproprion reduces craving in some smokers. Nicotine addiction has been reviewed recently at cellular and systems levels [38-41]. 

Saint-John s-wort was used in ancient Greece and medieval Europe, where it was believed to ward off evil spirits. Its name derives from wort, the Old English word for herb, and the fact that it was harvested in Europe on the eve of St. John s day (June 24th) and burned to purify the air (Fleiligenstein and Guenther 1998). Traditional uses include treatment of depression, insomnia, enuresis, and anxiety. Modern use has focused on its antidepressant effects and possible antiviral effects for treatment of the human immunodeficiency virus (FIIV) (Fleiligenstein et al. 1998) (table 7.3). There has been some interest in its antiglioma effects as well (Couldwell et al. 1993). 

In addition, whenever an antidepressant that blocks serotonin reuptake is discontinued, an unpleasant but harmless discontinuation syndrome manifested by abdominal discomfort, instability, anxiety, and occasionally painful shock-like sensations in the extremities can arise. The risk appears to be greatest with venlafaxine and paroxetine. Consequently, switching from one of these medications to another that does not block serotonin reuptake requires a gradual taper of the first medication over days to weeks. 

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. 

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... 

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 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. 

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