Medication for Anxiety

The use of medication is a critical issue among those who struggle with anxiety on a daily basis, as well as for professionals treating anxiety disorders. For many people, medication is a positive turning point along the path to recovery. For others, medication can confuse and complicate the recovery process, when freedom from anxiety is purchased at the cost of long-term addiction to tranquilizers. For still other people—those who are either phobic of or philosophically opposed to all types of drugs—medication may seem not to be an option, even when it's needed. One thing is clear: The pros and cons of relying on medication are unique and variable in each individual case.

If you feel your problem with anxiety is relatively mild (if it's more of an inconvenience or nuisance instead of a debilitating or highly distressing condition), you may want to consider cognitive behavioral therapy (as described on this site) and/or natural approaches first before trying prescription medication. Natural approaches include regular, preferably aerobic exercise, a practice of regular deep relaxation (for example, a recorded relaxation visualization or meditation), stress management, simplifying your life, and natural herbs or supplements which have a relaxing effect. More information on all of these approaches is available in any of my self-help books (see self-help books button).

On the other hand, if you have a more severe problem with anxiety, appropriate use of medication may be an important part of your treatment. This is particularly true if you're dealing with panic disorder, agoraphobia, or obsessive-compulsive disorder. It's also true for social phobia and generalized anxiety disorder when these problems interfere with the quality of your life in a major way. Approximately 50 to 60 percent of my clients take medication. For them, my impression is that a combination of therapy, natural methods and medication provides the most helpful, effective, and compassionate approach to recovery.

Situations Where Medication is Appropriate

In my clinical experience, there are certain types of individuals, in certain types of situations, for whom medications are appropriate. What follows is a list of situations where medication might be appropriate, along with the types of medications that might appropriately be used.

  1. You have panic attacks that are so frequent (for example, one or more per day) and severe that they impede your ability to work and earn a living, your primary personal relationships, and/or your sense of basic security and control over your life. "Severe" means that you have difficulty functioning and/or are suffering considerable distress. Enduring severe levels of anxiety for long periods of time can, unfortunately, predispose your nervous system to stay anxious much longer than it would if the anxiety were reduced by medication early on. Two types of medication are most frequently used to treat panic attacks. The first type are antidepressants. Even though they're labeled "antidepressants," such medications also have a potent effect in reducing anxiety. The most commonly used antidepressants include SSRI medications such as Zoloft (sertraline), Luvox (fluvoxamine), Celexa (citalopram), or Lexapro (escitalopram). Sometimes instead of an SSRI (selective serotonin reuptake inhibitor), an SNRI (serotonin-norepinephrine reuptake inibitor) such as Effexor (venlafaxine) or Cymbalta (duloxetine) is used. Yet another class of antidepressant medications sometimes used are the tricyclics, such as Tofranil (imipramine) or Pamelor (nortriptyline). These days, however, they are a second choice after SSRIs or SNRIs have been tried. 


    The other type of medication used to treat panic (and other anxiety disorders) are the benzodiazepine tranquilizers. Among these, Xanax (alprazolam), Klonopin (clonazepam), or Ativan (lorazepam) are typically used. Usually, such drugs are prescribed for a period of six months to two years at a high enough dose to significantly reduce the frequency and severity of panic, as well as anxiety about panic.


  2. You are agoraphobic and have a difficult time undertaking real-life exposure to phobic situations (see the section on the basic treatment program for an explanation of exposure). That is, you've tried to do exposure for some time without medication and not gotten very far in facing fearful situations. Low doses of a benzodiazepine tranquilizer, such as Klonopin (not more than 0.25 to 0.5 mg per day), may enable you to negotiate graded exposure to your phobias. Higher doses, though, will interfere with the process of exposure. You need to feel at least mild anxiety while undertaking exposure for the technique to be effective. After exposure hierarchies have been completed with tranquilizers, it's important to rework them without medication, to ensure a full and permanent recovery from your phobias.
    The benefits of exposure are likely to be retained even after the medication is discontinued, if the dose has been sufficiently low. The SSRI antidepressants (see below), such as Zoloft (sertraline), Luvox (fluvoxamine), or Celexa (citalopram) can also be highly effective in helping people undertake exposure. In fact, many psychiatrists consider SSRI medications to be an essential part of the treatment of agoraphobia.

  3. You're dealing with acute anxiety in response to a crisis situation. You may benefit from relying on a benzodiazepine tranquilizer on a short-term basis to get you through a particularly stressful time (such as interviewing for a new job, dealing with a significant health crisis, the death of a close relative, or other such major life events). Alternatively, a sedative (Restoril or Ambien, for example) might be prescribed to help you sleep during such a time.

  4. If you have chronic or severe depression accompanying panic disorder, agoraphobia, obsessive-compulsive disorder or any other anxiety disorder, you will usually benefit from a prescription antidepressant medication. Milder cases of depression ( you do not lose your appetite, your ability to sleep, your interest in simple pleasures, and/or do not have suicidal thoughts) may respond to the herb St. John's wort, the supplement S-adenosyl-methionine (SAM-e), or amino acids such as tryptophan, tyrosine, or DL-phenylalanine. Moderate to severe cases of depression are best treated with an SSRI, SNRI, tricyclic, or other types of antidepressant medications. Such medications will help relieve depression, panic, and anxiety at the same time.

  5. If you suffer from performance anxiety in public speaking or other performance situations—especially if the anxiety involves heart palpitations, sweating or blushing—you may be helped by short-term doses of beta-blocking drugs, such as Inderal (propranolol). A benzodiazepine tranquilizer, such as Xanax or Klonopin, may also be used on occasion (not regularly) to help you negotiate high performance situations.

  6. Difficult cases of social phobia or social anxiety (for example, you avoid a wide range of social situations or you are unable to attend important meetings at work) may be helped by SSRI antidepressant medications. These medications should be taken in conjunction with individual or, preferably, group cognitive-behavioral therapy.

  7. Obsessive-compulsive disorder often benefits from the use of antidepressant medication, usually in combination with cognitive therapy, exposure, and response prevention. Medications such as Anafranil (clomipramine), Prozac (fluoxetine), or Luvox (fluvoxamine) are frequently used in the treatment of this disorder. Sixty to seventy percent of persons with obsessive-compulsive disorder experience an improvement in their symptoms while taking one of these drugs. All of these medications appear to be helpful in treating obsessive-compulsive disorder itself, whether or not it is accompanied by depression. Anafranil, however, does have some undesirable side effects.
Types of Medication Used to Treat Anxiety Disorders

What follows is a description of the major classes of prescription medications used in the treatment of anxiety disorders. Potential advantages and drawbacks of each type of medication are considered.

SSRI Antidepressant Medications

The SSRI (selective serotonin reuptake inhibitor) antidepressant medications include Prozac (fluoxetine), Zoloft (sertralene), Luvox (fluvoxamine), Celexa (citalopram), and Lexapro (escitalopram) among others. In the past twenty years, they have become the first-line medications used by most psychiatrists to treat anxiety disorders. The SSRIs all increase levels of the neurotransmitter serotonin in the brain by preventing the reabsorption of serotonin at synapses (spaces between nerve cells). With increased serotonin, the number of serotonin receptors on nerve cells in the brain can decrease (not as many are needed). The reduction in serotonin receptors takes place over the first month or two of taking an SSRI and is technically called "downregulation." Downregulation allows the millions of nerve cells in the serotonin receptor system (particularly those in parts of the brain responsible for anxiety) to become less sensitive to changes in the neurochemical environment of the brain created by stress. That means less dramatic shifts in mood and less vulnerability to anxiety.

The SSRIs tend to be as effective—sometimes more effective—than the older tricyclic antidepressants that have been used to treat panic (e.g., imipramine, desipramine, nortriptyline). They also have the distinct advantage of causing fewer side effects for most people than the older antidepressants. SSRIs are used most often to treat panic, panic with agoraphobia, or obsessive-compulsive disorder. They have also found use with social phobia, particularly generalized social phobia, where a person is phobic of most types of social situations and encounters. Sometimes they are used to treat post-traumatic stress disorder or generalized anxiety disorder, especially when these difficulties are accompanied by depression. People differ quite a lot in their response to the SSRIs. If you try one and experience no benefit, be willing to try another. To gain full benefit from an SSRI, you may need to take it for six months to two years. Typical effective daily doses for SSRIs are: Prozac, 20 to 40 mg; Zoloft, 50 to 200 mg; Luvox (fluvoxamine), 50 to 200 mg; Celexa 20 to 60 mg, and Lexapro, 10 to 20 mg. Effective doses of these medications for OCD are at the high end of these dose ranges. However, some clients find that they obtain good results from lower doses. It typically takes at least four weeks at a normal dose for an SSRI medication to achieve therapeutic benefits.

Advantages
The SSRIs can be helpful for any of the anxiety disorders or depression. They are particularly helpful for persons with severe panic disorder, agoraphobia, or obsessive-compulsive disorder. SSRIs are easily tolerated and safe for medically ill or elderly persons. They have less likelihood of causing addiction. They do not cause problems when taken long term. In most cases, they do not lead to weight gain.

Drawbacks
Although SSRIs have fewer side effects than the older cyclic antidepressants, they can cause side effects in some people, including: jitteriness, agitation, restlessness, dizziness, drowsiness, headaches, nausea, gastrointestinal distress, and sexual dysfunction. These side effects tend to go away after two weeks, so it's important to try to ride them out during the early phase of treatment. All of these side effects can be minimized by starting off with a very low dose of the medication and increasing it, over time, to therapeutic levels. For example, doses might start as low as 5 mg per day for Prozac or even Zoloft. To achieve such doses, you need to start with a small portion of a single tablet or capsule per day in most cases, then gradually increase up to one tablet or capsule per day over a period of two or weeks. Be willing to take plenty of time in increasing the dose gradually. (You may notice side effects increase for a day or two after each dose increase.)

Abrupt discontinuation of an SSRI medication can cause withdrawal symptoms, including low mood, lethargy, dizziness, irritability, and what have been described as "flu-like" symptoms. These symptoms can be minimized or eliminated by tapering down the dose gradually over a period of one month or, in some cases, longer.

One final drawback of SSRIs is their expense. Without insurance, you can pay upwards of $200 per month for some SSRIs. Generic versions are less expensive than brand names. The optimal duration for taking an SSRI medication is six months to two years. You increase your risk of a return of symptoms if you take the medication for a shorter time period.

Persons with bipolar disorder (manic depression) should only take SSRIs under the supervision of a knowledgeable physician, as they can aggravate manic states.

High-Potency Benzodiazepines

The high-potency benzodiazepine tranquilizers (BZs) Xanax (alprazolam), Ativan (lorazepam), and Klonopin (clonazepam) are commonly used to treat anxiety disorders. Older benzodiazepine drugs, such as Valium, Librium, or Tranxene are occasionally tried when a person is sensitive to the side effects of the newer BZs. The benzodiazepines are often used in conjunction with SSRI antidepressants (or older tricyclic antidepressants) to treat severe cases of panic disorder. Frequently, it's possible to gradually withdraw from use of the BZ after the antidepressant medication has achieved its full antianxiety benefit (i.e., four to six weeks).

Benzodiazepine drugs generally depress the activity of the entire central nervous system and thus directly and efficiently decrease anxiety. They do so by binding with receptors in the brain that function to tone down or suppress activity in those parts of the brain responsible for anxiety—the amygdala, locus ceruleus and limbic system in general. At higher doses, BZ tranquilizers act like sedatives and may promote sleep. Lower doses tend to simply reduce anxiety without sedation. The main difference between various benzodiazepines is each medication's "half-life," or the length of time their chemical metabolites stay in your body (for example, Xanax has a half-life of eight hours, Klonopin eighteen to twenty-four hours, and Valium forty-eight to seventy-two hours).

At present the most common tranquilizer used to treat anxiety disorders is Xanax (alprazolam). Alprazolam differs from other BZs in that it has an additional antidepressant effect, as well as the ability to relieve anxiety. It also tends to have a less sedating effect than other tranquilizers. Because Xanax has a short half-life, two or three doses per day are usually prescribed. If you take only one dose per day, you may experience "rebound anxiety"—the tendency to experience heightened levels of anxiety as the medication wears off. BZs with longer half-lives, such as Klonopin, tend to cause less rebound anxiety and can often be taken in a single dose per day. An extended-release form of  Xanax, Xanax XR, is currently used as an alternative to Klonopin.

Advantages
BZs work very quickly, reducing symptoms of anxiety within fifteen to twenty minutes. Unlike antidepressants, which need to be taken regularly, BZs can be taken on an "as needed basis" only. That is, you can take a small dose of Xanax, Ativan, or Klonopin only when you have to confront a challenging situation, such as a graded exposure task, going to a job interview, or taking a flight.

The BZs tend to have less bothersome side effects for many people than the antidepressant medications (especially the tricyclic antidepressants). Sometimes they are the only medication that can provide relief when a person is unable to take any of the antidepressant medications. Generic forms of BZs are available, reducing their cost.

Drawbacks
BZ medications, unlike antidepressant medications, are often addictive. Regardless of the dose, if you take a BZ medication daily for more than two or three weeks, you run a risk of becoming both psychologically and physically dependent. Physical dependency means that if you stop taking the medication abruptly, severe anxiety symptoms are likely to occur. Many people who have taken Xanax (or other BZs) for longer than a month report that it's very difficult getting off the medication. Abrupt withdrawal from these medications is dangerous and may produce panic attacks, severe anxiety, confusion, muscle tension, irritability, insomnia, and even seizures. A more gradual tapering of the dose, stretched out over many weeks or even months, is what makes withdrawal possible. People vary in the ease with which they can withdraw from BZs, but as a general rule, it's best to taper off very gradually over a period of several months. During this withdrawal period, you may experience a recurrence of panic attacks or other anxiety symptoms for which the drug was originally prescribed. If a BZ medication is tapered off too quickly, you can experience rebound anxiety Unfortunately, sustained rebound anxiety may lead to relapse: a return of your anxiety disorder at equal or greater severity than what you experienced before taking the medication. To minimize the risk of rebound, it is critical to withdraw from your dose of a BZ very gradually, preferably over several months under the supervision of your prescribing physician.

Another drawback of BZs is that they are effective only as long as you take them. When you stop taking them, your anxiety disorder has virtually a 100 percent chance of returning, unless you have learned coping skills ( relaxation, exercise, stress management, working with self-talk, assertiveness, and so on) and made lifestyle changes that will result in long-term anxiety relief. Taking a BZ only, without doing anything else, amounts to merely suppressing your anxiety symptoms without getting at the cause of your difficulty.

Long-term use of BZs (more than two years) is sometimes necessary in certain cases of severe panic or anxiety that does not respond to any other type of medication. While enabling many people to function, long-term BZ use has several problems. Many long-term BZ users, especially those taking higher doses, report that they feel somewhat depressed and/or less vital and energetic than they would like. It is as though the medication tends to sap them of a certain degree of energy. Often, if they are able to switch to an antidepressant medication to help manage their anxiety, they regain a sense of vitality and enthusiasm for life. As a general rule, the BZs are most appropriate for treating short-term, acute anxiety and stress rather than longer-lasting conditions, such as agoraphobia, post-traumatic stress disorder, or obsessive-compulsive disorder. Wherever possible, chronic, long-term anxiety disorders are most appropriately treated with SSRI antidepressants. There are, however, certain individuals who seem to need to take a low-dose of a BZ over the long term in order to function. They accept the addiction and other side effects in exchange for protection from the anxiety that they have been unable to manage using solely natural techniques or other types of medication. If you are over fifty years old and have been taking a BZ medication for more than two years, you should periodically receive medical checkups, including an evaluation of liver function.

Serotonin-Norepinephrine Reuptake Inhibitor (SNRI) Antidepressants

SNRI antidepressants work by blocking the reuptake of two major neurotransmitters, serotonin and norepinephrine. At present, the three most commonly used SNRIs are Cymbalta (duloxetine), Effexor (venlafaxine), and Pristiq (desvenlafaxine). Desvenlafaxine is the mirror-image isomer of venlafaxine, and is claimed by some to have fewer side effects than venlafaxine, though there is no systematic research on this. The SNRIs are potent medications and may be tried when response to SSRIs is insufficient. They are most commonly used to treat depression and/or generalized anxiety disorder but may be used to treat other anxiety disorders such as panic disorder or OCD.

The main advantage of SNRIs over the SSRIs is that they can stabilize both the norepinephrine and serotonin receptor systems, instead of just the serotonin system alone. So for certain people, they are more powerful anxiolytics than the SSRIs. They have the same disadvantages as the SSRIs, with side effects including dizziness, nausea, weakness, dry mouth, insomnia, and sexual dysfunction. Like the SSRIs, the dose needs to be tapered gradually when SNRIs are discontinued. Abrupt discontinuation is associated with withdrawal symptoms.

Serotonin Modulator and Stimulator (SMS) Antidepressants

SMS antidepressants are a relatively new class of medications which, in addition to promoting serotonin reuptake inhibition like SSRIs, also stimulate transmission at one or more serotonin receptor sites.

Viibryd (vilazodone), with a normal dose range of 10-40 mg. per day, facilitates the serotonin receptor 5-HT1A, a mechanism of action it shares with the anxiolytic medication Buspar (busiprone) as well as the atypical antipsychotic medication Abilify (aripipraxole).

Viibryd was approved in early 2011 for use in the United States. In September 2011, the FDA raised questions about whether Viibryd showed any advantage over previously and commonly available SSRIs. Some users have reported good results with Viibryd, both with respect to anxiety and depression, while others have reported side effects such as a nausea, diarrhea, sleeplessness, and weight gain leading them to discontinue the drug. Viibryd was marketed as having less sexual side effects than other SSRIs, though results so far have shown that this benefit is not invariably reported.

Brintellex (vortioxetine), with normal dose range 5-20 mg. per day, was introduced in the U.S. in late 2013. It is described as a multimodal antidepressant because it has a differential action on different types of serotonin receptors. Specifically, it has an antagonistic (inhibitory) reaction toward serotonin 5-HT3A and 5-HT7 receptors, while it tends to facilitate neurotransmission at 5-HT1A and 5-HT1B receptors. It’s also a potent serotonin reuptake inhibitor like typical SSRIs.

Preliminary research indicates that these multiple effects on several different serotonin receptors result in increased noradrenaline (as in SNRIs) and dopamine (as in mood stabilizers) as well as increased glutamine transmission. So the drug appears to have a variety of effects beyond that of simple serotonin reuptake inhibition.

Brintellex is currently being studied for potentially beneficial cognitive effects, apart from its antidepressant effects, in elderly persons.

Tricyclic Antidepressants

Tricyclic antidepressants include Tofranil (imipramine), Pamelor (nortriptyline), Norpramin (desipramine), Anafranil (clomipramine), Elavil (amitriptyline), and Sinequan (doxepin), among others. These medications (especially imipramine) are frequently used to treat panic attacks, whether such attacks occur by themselves or in conjunction with agoraphobia. Tricyclic antidepressants seem to reduce both the frequency and intensity of panic reactions for many people. They are also effective in reducing the depression that often accompanies panic disorder and agoraphobia. While it used to be believed that Tofranil was the most effective antidepressant for treating panic, more recent evidence indicates that any of the tricyclic antidepressant medications can be helpful, depending on the individual. Anafranil tends to be specifically helpful in treating OCD.

The tricyclic antidepressants are used less these days than SSRI antidepressants because they tend to have more troublesome side effects. For example, in studies of imipramine, usually about one-third of the subjects drop out because they cannot tolerate side effects (only about 10 percent do in studies using SSRIs). On the other hand, tricyclic antidepressants are sometimes a better choice than SSRIs for certain people because most of them (other than Anafranil) modify a different receptor system in the brain (the noradrenergic system instead of the serotonin system). As with SSRIs, tricyclic antidepressants are best tolerated by starting with a very low dose (for example, 5 mg per day of imipramine) and gradually working up to a therapeutic dose level (approximately 100 to 200 mg per day).

Advantages
Tricyclic antidepressants, like the SSRIs, do not lead to physical dependence. They have a beneficial effect on depression as well as on panic and anxiety. They block panic attacks, even if you are not depressed. Because generic forms are available, they are inexpensive.

Drawbacks
Tricyclic antidepressants (unlike SSRIs) tend to produce anticholinergic side effects, including dry mouth, blurred vision, dizziness or disorientation, and postural hypotension (causing dizziness). Weight gain and sexual dysfunction can also occur. With imipramine, in particular, anxiety may increase during the first few days of administration. With clomipramine (effective for OCD), side effects can be particularly bothersome.

Although these side effects tend to diminish after one or two weeks, they persist for 25 to 30 percent of people who take tricyclic antidepressants after the initial adjustment period.

Like the SSRIs, tricyclic antidepressants take about three to four weeks to offer therapeutic benefits. While able to block panic attacks, these medications may not be as effective as SSRIs and benzodiazepine tranquilizers in reducing anticipatory anxiety about the possibility of having a panic attack or having to face a phobic situation.

Finally, about 30 to 50 percent of people will relapse (experience a return of panic or anxiety symptoms) after discontinuing tricyclic antidepressant medications. This is, however, a much lower relapse rate than occurs when benzodiazepines are discontinued.

Other Antidepressants

Other antidepressant medications occasionally used with anxiety disorders include Remeron (mirtazapine), Wellbutrin (bupropion), Serzone (nefazodone), and Desyrel (trazodone). Remeron is classified as a noradrenergic/specific serotonergic antidepressant (NaSSA), and, like Effexor, it has a dual action, increasing the levels of both norepinephrine and serotonin at the synapse. Remeron is very sedating at lower doses and may be used to promote sleep. At higher doses, it is an effective antidepressant, and may be used when Effexor is not well tolerated. Psychiatrists sometimes use it in combination with an SSRI, like Paxil or Celexa, to enhance the antianxiety and/or antidepressant effects of the SSRI, a strategy called augmentation.

Wellbutrin is often helpful for depression but can be difficult for people with anxiety disorders to tolerate, since its side effects can include anxiety and insomnia. On the positive side, Wellbutrin is the only newer antidepressant that does not have sexual side effects.

Serzone was widely used in the 1990s as both an antidepressant and an antianxiety medication but has fallen out of favor because of reports of liver damage or failure associated with its usage. Trazodone is an older antidepressant medication that has been around since the early 1980s. While not frequently prescribed for anxiety, it can be a highly effective sedative for many people. It has the advantage of not being addictive, like sedatives such as Restoril, Ambien, or Lunesta, and may be more potent for some people than natural sedatives like melatonin and tryptophan. Its side effects are similar to those listed for the tricylic antidepressants.

There are several other classes of medications used to treat anxiety disorders, such as beta blockers ,for example, Inderal (propranolol), mood stablizers, particularly Neurontin (gabapentin), and Buspar (buspirone) . For further information on medications, including how long to take them and how to discontinue them, see the chapter on medications in The Anxiety & Phobia Workbook.