Anxiety Disorders

Description

Alternative Names

Medications

Until recently, the anti-anxiety drugs known as benzodiazepines were the primary medications for anxiety. Increasingly, antidepressants, particularly the selective serotonin-reuptake inhibitors (SSRIs), are being used as the initial treatment. They are proving to be effective, nonaddictive, and to have relatively minor side effects.

Many standard antidepressants take two to four weeks, and sometimes up to 12 weeks, before they are fully effective. People who take them may also experience a temporary period of increased anxiety. Consequently, about a third of patients stop taking antidepressants for anxiety disorders before completing the initial phase of therapy. A combination of a benzodiazepine and an antidepressant is sometimes used to avoid the initial anxiety symptoms and to hasten control of panic symptoms. The benzodiazepine can then be withdrawn and the antidepressant, with its negligible chance for long-term abuse, is continued.

No one should become disheartened if one drug treatment fails. Another may prove to be very effective, even it is a drug of a similar type. Drug combinations should be tried if a single drug and cognitive-behavior therapy has failed. Because many anxiety disorders are chronic, drug therapy sometimes is needed for prolonged periods, even years.

Antidepressants

Selective Serotonin Reuptake Inhibitors (SSRIs). Selective serotonin-reuptake inhibitors (SSRIs) are the first-line treatment of major depression and proving to be helpful for many anxiety disorders. They work by increasing levels of serotonin in the brain. SSRIs include fluoxetine (Prozac), sertraline (Zoloft), paroxetine (Paxil, Asimia), fluvoxamine (Luvox), citalopram (Celexa, Cipramil, and escitalopram (Lexapro). Escitalopram is derived from the active agent in citalopram and may have fewer side effects than other SSRIs.All these agents are proving to be very valuable for adults and even for many children with most anxiety disorders. The following are some indications for their use in specific anxiety disorders:

• Obsessive-Compulsive Disorder. SSRIs are the first-line treatment for obsessive-compulsive disorder (OCD). They reduce symptoms by 25% to 35% in about half of all patients. (SSRIs may be less effective with tics, hoarding, and compulsive behaviors than with other OCD symptoms.)
• Panic disorder. SSRIs may also be very useful in treating patients with panic disorder. Some -- but not all -- studies suggest that higher doses than those used for depression may be required in order to achieve benefits. More research is needed on the optimal dosages.
• Phobias. SSRIs may also help people with phobias, including agoraphobia and social phobias. Relapse is common in social phobia patients, and treatment for longer than a year may be needed in some patients. Combining medications with cognitive-behavioral therapy can help prevent relapse.
• Post-Traumatic Stress Disorder. SSRIs may help some people with post-traumatic stress disorder (PTSD). Their benefits may be limited. Victims of child abuse, for example, tend to respond poorly to SSRIs. A study on sertraline suggested that although it was particularly effective in women it may not offer many benefits for combat veterans. At this time sertraline (Zoloft) and paroxetine (Paxil) are specifically FDA-approved for PTSD, although studies suggest that other SSRIs may be helpful.
• Generalized Anxiety Disorder. SSRIs have been less studied for generalized anxiety, but studies on paroxetine (Paxil), sertraline (Zoloft), and escitalopram (Lexapro) suggest that SSRIs may be very effective for many people with GAD.
• Anxiety Disorders in Children. SSRIs appear to be effective for children who have both OCD and major depression. At this time, Prozac has been approved for children with OCD. Some evidence suggests SSRIs, may reduce symptoms of social phobia, separation anxiety disorder, or generalized anxiety disorder in children and teens. Still, controversy remains about when and if young people with anxiety disorders should be given drugs.

SSRIs can cause agitation, nausea, and sexual dysfunction (including delay or loss of orgasm and low sex drive; taking a supervised drug "holiday" on the weekend may improve sexual function during that time, although it may also cause dizziness, exhaustion, and depression.) Over time, many SSRI-treated patients gain weight, although the degree of weight gain may vary depending on the agent. For example, paroxetine appears to pose a greater risk for weight gain than citalopram. Elderly people taking these drugs should take the lowest effective dose possible, and those with heart problems should be monitored closely.

Side effects in children are similar to those in adults. In addition, there is some concern that SSRIs may limit growth in children. Although there have been reports of a greater risk for suicide in young people taking Paxil, the evidence supporting such reports is weak. Intensive research is underway to determine if SSRIs pose a risk for suicide in anyone.

Designer Antidepressants. A number of newer antidepressants that target other neurotransmitters alone or in addition to serotonin are proving to be very promising for anxiety, including generalized anxiety disorder. They include nefazodone (Serzone), venlafaxine (Effexor), and mirtazapine (Remeron).

• Venlafaxine (Effexor) is very effective for both short- and long-term treatment of generalized anxiety disorder. It may have some benefits for social anxiety. As with the SSRIs, and unlike other newer antidepressants, venlafaxine impairs sexual function. Of concern are reports of changes in blood pressure and heart conduction abnormalities, which may cause serious problems in elderly patients. Some patients report severe withdrawal symptoms, including dizziness and nausea.
• Nefazodone (Serzone) has shown some effectiveness in patients with GAD, social phobias, and panic disorder. The drug is more rapidly effective and has fewer distressing side effects, including sexual dysfunction, than SSRIs. Nefazodone is one of the only antidepressants that has a positive effect on sleep efficiency, which may particularly benefit patients with insomnia. The drug may cause an abrupt drop in blood pressure after standing up suddenly. Of concern are rare cases of liver failure in patients taking nefazodone.
• Mirtazapine (Remeron) may be an effective treatment for panic disorder, generalized anxiety disorder, obsessive-compulsive disorder, and even posttraumatic stress disorder. In addition to taking it orally, mirtazapine is now available as a tablet that dissolves on the tongue. It may be more rapidly effective than other SSRIs and has stronger early actions against anxiety in patients who also suffer depression. It may cause less sexual dysfunction than some other antidepressants. It interacts with histamine, a chemical involved in allergic responses; these actions can cause drowsiness, which may make it a useful drug for patients who suffer from insomnia. The drug also causes blurred vision. The drug has been associated with weight gain, although in one study it was not significant. It does not appear to have the adverse acute effects on the heart that other newer antidepressants have, although it may elevate cholesterol and triglyceride levels slightly.

Tricyclic Antidepressants. The antidepressant drugs known as tricyclic antidepressants (TCAs) have also been effective in treating panic and obsessive-compulsive disorders. Studies on specific TCAs have suggested the following benefits:

• Imipramine (Tofranil, Janimine) is the most commonly used TCA for panic disorder. It is also effective in treating agoraphobia and GAD. In one study it was helpful in reducing side effects during withdrawal from benzodiazepines, the standard anti-anxiety agents.
• Doxepin (Adapin, Sinequan) has been beneficial for people with a mix of generalized anxiety disorder and depression.
• Clomipramine (Anafranil) is also effective for panic disorders and has been approved for OCD. The drug causes significant reduction in OCD symptoms for patients, including some children, who can tolerate it. (The other tricyclics do not appear to benefit OCD patients.) Many patients stop using Anafranil, however, because of side effects. Many of those who stay on the drug experience adverse effects.

Side effects of TCAs include sleep disturbance, abrupt reduction in blood pressure upon standing, weight gain, sexual dysfunction, and mental disturbance. Elderly patients and those with a history of seizures, cardiac problems, closed-angle glaucoma, and urinary retention or obstruction should be closely supervised when taking tricyclics.

Monoamine Oxidase Inhibitors. Monoamine oxidase inhibitors (MAOIs), typically phenelzine (Nardil) or tranylcypromine (Parnate), are antidepressants used for panic disorder or OCD that does not respond to other treatments. Moclobemide (Manerix, Aurorix) is a newer MAOI available in Canada and Europe that showed some benefits for social phobias in some, but not all studies.

MAOIs commonly cause weight gain, drowsiness, dizziness, sexual dysfunction, and insomnia. The primary problem with most of these agents is the need for dietary restrictions. Severe hypertension can be brought on by eating certain foods that have a high tyramine content, including cheese, red wine, vermouth, dried meats and fish, canned figs, and fava beans. MAOIs can also lead to serious hypertensive interactions with certain drugs, including some common over-the-counter cough medications and decongestants. They can also cause birth defects and should not be taken by pregnant women.

Benzodiazepines

Benzodiazepines are effective medications for most anxiety disorders and have been the standard of treatment for years. However, their use has been associated with a high risk for dependency and abuse. (Some reports suggest they are harder to withdraw from than heroin.) Therefore, they have been supplanted in most cases by SSRIs and by newer antidepressants. Benzodiazepines include the following:

• Alprazolam (Xanax) and clonazepam (Klonopin) are effective for panic disorder, some phobias, and generalized anxiety disorder. Benzodiazepines in combination with selective serotonin reuptake inhibitors may be particularly helpful in the treatment of panic attacks, although there is no standard as yet for the safest and most effective method for administering this combination.
• Other benzodiazepines, including diazepam (Valium), lorazepam (Ativan), and chlordiazepoxide (Librium), are used mainly for generalized anxiety.

Side Effects. Benzodiazepines have many side effects. The most common are daytime drowsiness and a hung-over feeling. In rare cases, they actually cause agitation. Some respiratory problems may be exacerbated by their use. The drugs appear to stimulate eating and can cause weight gain. In one 2002 study, 33% of patients experienced incontinence at least twice a week. Highest risk was in long-acting agents, such as Librium. Benzodiazepines can interact with certain drugs, including cimetidine (Tagamet), antihistamines, and oral contraceptives. Benzodiazepines are potentially dangerous when used in combination with alcohol. Overdoses can be serious, although they are very rarely fatal.

The elderly are more susceptible to side effects and they should usually start at half the dose prescribed for younger people. The drugs increase the risk of falling, and some studies have reported a higher risk for hip fracture in older people who take the drugs, although this may occur only with certain benzodiazepines (e.g., lorazepam) or with the use of more than one. In any case, more research is needed. Also of concern are studies showing a high risk of automobile accidents in people who take benzodiazepines. Benzodiazepines taken during pregnancy are associated with birth defects, and they should not be used by pregnant women or by nursing mothers.

Loss of Effectiveness and Dependence. Eventually these drugs can lose their effectiveness with continued use at the same dosage. As a result, patients may want to increase their dosage to prevent anxiety. This causes dependency, which can occur after as short a time as several weeks of taking these agents. It should be noted, however, that patients with generalized anxiety disorder rarely become tolerant to their effects. Some evidence suggests that the risk for abuse exists only in people who are already susceptible to substance abuse.

Withdrawal and its Treatments. Withdrawal symptoms can be very severe, even in people who rapidly discontinue benzodiazepines after taking them for only four weeks. There are some reports that benzodiazepines are harder to withdraw from than heroin. Symptoms include sleep disturbance and anxiety, which can develop within hours or days after stopping the medication. Some patients experience stomach distress, sweating, and insomnia, which can last from one to three weeks. The longer the agents are taken and the higher their dose, the more severe these symptoms can become. Simply tapering off gradually helps about 60% of people to withdraw. Certain medications (anti-seizure agents, antidepressants, buspirone) may be helpful.

Azapirones

Azapirones, including, buspirone (BuSpar) and gepirone (Ariza, Variza), act on serotonin receptiors call 5-HT(1A). Buspirone has been the most intensively studied. It appears to be as effective as a benzodiazepine for treating generalized anxiety disorder. Some experts also think it may be useful for adolescents and children. It usually takes several days to weeks for the drug to be fully effective, and it is not useful against panic attacks.

It should be noted that the drug does not produce any immediate euphoria or change in sensation, so some people believe, erroneously, that the drug doesn't work. Such qualities result in a very low potential for abuse. In fact, unlike the benzodiazepines, buspirone is not addictive, even with long-term use, so it may be particularly useful for the patient whose anxiety disorder coexists with alcoholism or drug abuse.

Buspirone also seems to have less pronounced side effects than benzodiazepines and no withdrawal effects, even when the drug is discontinued quickly. Common side effects include dizziness, drowsiness, and nausea. BuSpar should not be used with monoamine oxidase inhibitors (MAOIs).

Beta-Blockers

Beta-blockers, including propranolol (Inderal) and atenolol (Tenormin), block the nerves that stimulate the heart to beat faster. They affect only the physiologic symptoms of anxiety and are most helpful for phobias, particularly performance anxiety. Beta-blockers are less effective for other forms of anxiety.

Clonidine

Clonidine, a drug that relaxes blood vessels, has been used to treat children with post-traumatic stress disorder. Some experts believe it should be tried for anxiety disorders if other therapies fail. The drug can have severe side effects.

Atypical Antipsychotics

In certain severe cases, agents called atypical antipsychotics may be useful. They include risperidone (Risperdal), olanzapine (Zyprexa), quetiapine (Seroquel), ziprasidone (Zeldox, Geodon), and others. In one study, risperidone was useful in combination with an SSRI for OCD patients who did not respond to an SSRI alone. They also may useful for severe GAD. Common side effects include sleepiness and dizziness. Most cause weight gain. In high doses they may cause extrapyramidal symptoms, which involve the nerves and muscles controlling movement and coordination. The risk for these side effects, however, are far less than with older antipsychotic agents.

Drugs Being Evaluated for Anxiety States

Gabapentin and Other Anti-Epileptic Agents. Gabapentin is a drug used for epilepsy. Small studies suggest it may be useful for certain anxiety disorders, such as social phobia and post-traumatic stress disorder. It may also be helpful during withdrawal from benzodiazepines. Pregabalin is an investigative agent that is similar to gabapentin and is showing promise for social phobia, panic disorder, and generalized anxiety disorders.

Hydroxyzine. Hydroxyzine (Atarax, Vistaril) is an antihistamine used to treat itching from allergies. In one well-conducted 2003 study, it was as effective as a benzodiazepine for treating GAD.

Prazosin. Prazosin (Minipress) is known as an alpha (or adrenergic) blocker. It reduces blood pressure and is sometimes used in benign prostate hyperplasia. Studies are supporting its effectiveness for alleviating nightmares and other symptoms in people with PTSD.

Immunotherapies for Strep-Related Obsessive-Compulsive Disorder. In cases of OCD originating with a strep throat infection during childhood, some studies are using therapies that affect the immune system. They include immunoglobulin treatments (injections of certain antibody groups), penicillin, corticosteroids (prednisone), and plasmapheresis (blood exchange). In one study, children with a first episode of OCD related to strep throat were treated with antibiotics, and OCD symptoms resolved in all of them. Other studies using antibiotics on patients with long-standing OCD have not reported success.