Patients with separation anxiety disorder have a fear of leaving a close relationship, such as the parent or home situation. Separation anxiety begins in childhood, and may or may not continue later on in life. It may manifest itself for the first time in kindergarten, with the child hanging onto the mother. Approximately, 5 % of the adult population has had the symptoms of separation anxiety. Separation anxiety may morph into a panic disorder or GAD.

Panic attacks occur with a number of physical symptoms that may include feelings of choking, trembling, diaphoresis, racing heart, shortness of breath, chest pain, fears of losing control or dying, numbness, chills or flushing, dizziness, lightheadedness, or fainting. Panic attacks usually reach their peak quickly, and last minutes to 1 or 2 h. While they may be triggered by situations such as having to speak in public, they often occur without any obvious external trigger. Panic attacks may occur with agoraphobia, which involves a fear of situations where escape is not easy. These include public places and crowds, public transportation, highway driving, being on a bridge, or in an elevator or other enclosed space, being far from home or alone, or being stuck at a party. Agoraphobia such as this may occur without panic disorder.

GAD involves excessive worrying, which may be about school, work, family, health, finances, or the outside world. With GAD, most people worry on a daily basis, not just occasionally. To diagnose GAD, the worrying must have been present for at least 6 months. People with GAD do not worry about just one facet of life, but many things. The worry becomes completely out of proportion to the significance of the problems. They also feel the physical aspects of anxiety, such as feeling “keyed up,” having concentration problems, insomnia, irritability, anger, or fatigue. Approximately, 5–6 % of the population suffers from GAD. It is more common in women than in men.

Social anxiety disorder is common during adolescence, particularly with the onset of dating, parties, and other social events. It may persist into the adult years. Public speaking is difficult for those with Social anxiety disorder, and this and other triggers can lead to avoidant behavior. Approximately 12 % of the population experiences Social anxiety disorder at some point.

OCD often has an onset in early adolescence. The obsessions are intrusive, and distressing thoughts become focused on one or more concerns: germs or other contaminants, a need to have things arranged perfectly, a fear of hurting someone close, somatic (body) obsessions, hoarding, or sexual or religious obsessions. Compulsions are actions that reduce the person’s anxiety somewhat, and are triggered by the obsessions. Compulsions can take the form of obsessive checking (particularly things like locks or a stove), repeated cleaning routines, repetition of words, prayers or actions, counting, or arranging objects over and over. As with most anxiety symptoms, OCD may wax and wane over time.

Pharmacotherapy is important in treating anxiety, but it is by no means the only treatment. For those with severe pain and psychologic comorbidities, “it takes a village” to treat a patient, which may include psychotherapists, yoga or Pilates instructors, biofeedback specialists, etc.

Taking medicine alone is considered passive coping and is not sufficient for those with severe anxiety. People are best off when they exercise regularly, and learn relaxation techniques, whether they are based in yoga, Pilates, tai chi, deep breathing, biofeedback, or meditation. We need to promote this “active coping” as a vital component of treating chronic pain and anxiety . The addition of psychotherapy, primarily cognitive/behavioral, is also important. It is vital to locate an excellent therapist, and for the patient to stick with that therapist for at least 4–6 months. While short-term therapy is better than no therapy, we believe that the ideal timeframe is 1 or more years. It takes some time to integrate the ideas of therapy into our lives. Self-help books, while somewhat useful, do not replace a great therapist; neither does talking to a close friend or relative. A great therapist can be life changing.

Benzodiazepines are a well-recognized treatment for anxiety, and are best used for acute anxiety, or a panic attack. Alprazolam is the most effective benzodiazepine for panic attacks, and is best used on an “as needed” basis. The lowest effective dose should be used; usual doses are 0.25–1 mg (start with ½ or 1 of the 0.25 mg tablets) as needed. Alprazolam should be limited and the patient closely monitored for overuse. Limited quantities should be prescribed.

At times, in a minority of patients, daily benzodiazepines are warranted. The usual situation is when the patient cannot tolerate nonaddicting approaches, such as the antidepressants. For insomnia, the occasional patient will only do well with a benzodiazepine, such as clonazepam (Klonopin). Diazepam (Valium) has antianxiety and muscle relaxant properties. Patients must be warned of the dangers of overuse and of combining these agents with alcohol or opioids, as well as the difficulty patients may encounter on withdrawal. For some highly anxious patients, the only medication tolerated is a benzodiazepine.

The older tricyclic antidepressants (TCAs) are more useful for certain types of pain (particularly headaches) than are the SSRIs or SNRIs. We will often use a TCA in anxious pain patients in an attempt to treat both their anxiety and migraine in order to minimize medication use. The prototype tricyclic is amitriptyline (Elavil). Amitriptyline is inexpensive, and is useful for chronic daily headache, migraine , neuropathy, fibromyalgia, etc. We recommend that clinicians start with very low doses of amitriptyline, taken at night, 5 mg (½ of a 10-mg tablet), slowly increasing to 20 or 25 mg per day. Doses may be increased to 100 mg (or more), but side effects may limit its usefulness. These include sedation, dry mouth, constipation, dizziness, weight gain, and urinary retention. Other TCAs include nortriptyline, a milder form of amitriptyline; doxepin, which has fewer side effects and is helpful for insomnia; and protriptyline (Vivactil). Protriptyline is one of the few TCAs that does not cause weight gain, but anticholinergic effects limit its use.

Because of the potential for adverse events, the newer SSRIs and SNRIs are often favored over the older TCAs. The major SSRIs differ somewhat in their side effect profile. Some patients do extremely well with one SSRI, but not with another. The most common side effects include nausea, spaciness, drowsiness or fatigue, dry mouth, anxiety, insomnia, decreased libido, impotence, asthenia, sweating, constipation, tremor, diarrhea, and anorexia. In addition, weight gain may be a major problem. In fact, weight gain and sexual side effects are the most common reason to discontinue an SSRI. Any of the SSRIs can decrease motivation.

Since many of the adverse events are dose related, one key to minimizing side effects is to begin with low doses—“start low and go slow” (Table 5.1). Minimizing the dose can, for instance, decrease the sedation or sexual side effects. Compliance is enhanced when the SSRIs are slowly titrated. The initial anxiety seen with SSRIs often abates if low enough doses are used.

At times, we will use a combination of older TCAs (usually at night) and SSRIs in the morning. One of the SNRIs, duloxetine, has several pain and GAD indications, making it a useful tool for treating the comorbid migraine patient. Table 5.2 highlights the SSRIs and SNRIs. In some patients, SSRIs actually exacerbate headaches. Fluoxetine is an inhibitor of the cytochrome P450 (CYP450) 2D6 system, and to a lesser extent, CYP450 3A4.

Fluoxetine (Prozac, generic) is available in 10, 20, and 40 mg pulvules; 10 mg scored tablets; or liquid (20 mg/5 mL). Prozac Weekly is a once per week capsule, equal to 20 mg daily. Fluoxetine is the prototype SSRI, having been used in tens of millions of people. Fluoxetine is a long-acting SSRI with a well-established track record. Its elimination half-life is 4–6 days, but the active metabolite, norfluoxetine, has an elimination half-life of 4–16 days. The long half-life is generally an advantage in avoiding the SSRI withdrawal syndrome. It is important to start with low doses of SSRIs; 5 or 10 mg of fluoxetine is a good starting point. Many patients report initial anxiety (or even panic) from SSRIs, and if they are on a low enough dose, they are less likely to discontinue the medication. Patients can begin with ½ a tablet of 10 mg fluoxetine. Over 4–10 days, the dose may be raised to 10 or 20 mg. The effective dose for migraine or tension headache varies widely, from 5 mg per day to 60 mg (or more). Formal studies on fluoxetine for headache prevention have yielded mediocre results. Most patients are on 20 mg daily. Milder tension-type headache often responds to low doses (10 or 20 mg). As is true with TCAs, lower doses of SSRIs are used for headache doses, sertraline is a CYP450 2D6 and 3A4 inhibitor. Sertraline (Zoloft, generic) is available in 25, 50, and 100 mg scored tablets. Sertraline is somewhat shorter acting; elimination half-life is 26 h of the parent drug and 62–104 h of the active metabolite. Because the half-life is shorter than with fluoxetine, patients are occasionally able to stop sertraline for 1 or 2 days and alleviate the sexual side effects. However, with the shorter half-life, withdrawal syndrome is occasionally seen with sertraline. I usually start with 25 mg, or ½ of a 25-mg tablet, and slowly increase; the average antidepressant dose is 75–150 mg, but the usual headache dose is approximately 50 mg. While many patients are on 100 mg or more for headaches, most patients are maintained on lower doses. The cost of the 50 and 100 mg tablets is approximately the same.