How Would You Manage This Woman Who is a Self Described 'Worry Wart'?

A 38 year old female lab technician is seen for “being nervous all the time”. She complains of being unable to relax. She relates to you that he has been a “worry wart” for as long as she can remember, always fearing that something is going to go wrong. Although her doctor has told her she is in excellent health, she relates that she sees him frequently for episodic stomach pains and palpitations.

She states she is always worrying about her children even when they seem to be doing well. She reports that she has a difficult time dropping off her 5-year-old daughter at school because of concerns something will happen to her while she is away.

What is the likely diagnosis?

The likely diagnosis is generalized anxiety disorder. However, since this is a clinical diagnosis, it is mandatory that other diagnoses be ruled out first. Looking at her thyroid function is critical, as thyroid disorders are common in women in this age group. Looking at blood pressure, and autonomic instability is also an important consideration l, as blood pressure lability may contribute to anxiety

symptoms.

Very rarely, this could be the presentation for a pheochromocytoma. Her palpitations, although likely from anxiety, could be a serious arrhythmia, and so this needs to be excluded. Furthermore, stomach pains may be from anxiety, but they may also be from dietary issues such as gluten sensitivity. In terms of alternative psychiatric diagnoses, the clinician should probe for depressive symptoms as well, as oftentimes anxiety symptoms mask an underlying depression.

Anxiety and depression often co-occur, so one must always keep both psychiatric diagnostic categories in mind. Further, the clinician should query her about specific obsessions and specific rituals, as she may not be forthcoming about her obsessive and/or compulsive symptoms, and she may have obsessive-compulsive disorder (OCD). Finally, it is important to screen for psychosis by determining whether she possesses insight that her anxieties are excessive. If she is convinced, for example, that her 5 year old daughter will meet harm in school, then one has to consider that what seems like anxiety, is in fact, paranoia.

What are the clinical features of generalized anxiety disorder?

The clinical features of generalized anxiety disorders (GAD) are a mental state dominated by anxieties in which the patient understands that she “worries too much” but that she feels she cannot “help it”. In other words, the patient does not believe that a catastrophe will happen, but the patient thinks that a catastrophe COULD happen, and this possibility dominates her thinking.

As a result, the patient is ruminative about catastrophes, but unlike OCD, the subject of the rumination changes. As the mental state is uncomfortable thinking about catastrophes, patients with GAD tend to isolate themselves because they realize this way of thinking makes others uncomfortable. With this social isolation can come depressive symptoms. Often, the anxiety is manifested by physical symptoms such as frequent urination, stomachaches, irritable bowels, headaches and/or fatigue. Physical illness should always be ruled out, as one can never assume these physical symptoms are psychologically based.

What diagnostic tests would you consider?

In terms of diagnostic tests, a CBC and TSH are critical. Other tests depend on the nature of the specific complaint. If there are GI symptoms, ruling out celiac disease is critical. If there are cardiac symptoms, ruling out an arrhythmia is also critical. If there are persistent headaches, then an imaging study should be considered.

What management options are available?

Management options include psychotherapy, such as CBT (cognitive behavioral therapy), and psychopharmacology. Within psychotherapy is psychoeducation, which helps the patient understand the nature and consequences of anxiety. Psychotherapy also includes lifestyle changes since sleeping well, eating well, and regular exercise can help anxiety symptoms.

Mindfulness based stress reduction (MBSR) is another psychotherapy tool which helps with GAD. This technique helps the patient understand that thoughts, like weather, comes and goes, and so paying attention to one’s thoughts helps the patient understand the temporary nature of these difficult feelings. If psychotherapy does not bring the patient to a sense of well-being, or if the situation is very intense, then psychopharmacology should be considered.

What would be your first-line drug therapy?

A selective serotonin receptor inhibitor (SSRI) is first-line, as this helps with ruminative thinking, with the least amount of side effects and no addiction potential. Amongst the SSRIs, sertraline (Zoloft®) would be my first-line, as this medication is well-tolerated and usually does not cause sedation or activation. Benzodiazepines are helpful, but the patient needs to understand that these are addictive. They are contraindicated in patients with a substance abuse problem. Small amounts of benzodiazepines can be used for “breakthrough” anxiety, as long as the patient understands that these

medications are to be used sparingly.

Other options include tricyclic antidepressants, serotonin-norepinephrine reuptake inhibitors (SNRIs), BuSpar and Inderal. Elavil, a tricyclic antidepressant can be given at low dose (10 mg), which will help with sleep, anxiety and mood. It can also alleviate bodily symptoms of muscle aches and pains. In the SNRI category, we have duloxetine (Cymbalta®), venlafaxine (Effexor®) and levomilnacipran(Fetzima®). Duloxetine and venlafaxine may be used to treat anxiety, but levomilnacipran is only FDA-approved for depression. These three drugs work on both increasing serotonin and norepinephrine in the brain, so we call these medications “dual action” drugs. In low dosages they work like SSRIs, and as the dose increases, the SNRI action increases. It is important to start these medications at low dosages, as an anxious patient will be very sensitive to the activating effect from norepinephrine.

Buspirone (BuSpar®) is a good option, either as a single agent, or in conjunction with an SSRI or an SNRI. Buspirone helps with rumination. Finally, propranolol (Inderal®) is a useful medication if the patient suffers from disabling palpitations or tremors secondary to anxiety. Propranolol 10 mg can be used on a daily or as needed basis, depending on the patient’s history.

How do you prescribe sertraline?

Sertraline should be started at 12.5 mg daily, which means that the patient takes a 25 mg tablet and cuts it in half. This dose is then titrated to efficacy, which means that the patient is followed up in 2-4 weeks, and if they are still symptomatic, the dose is increased by 12.5 mg at each visit, with a maximum of 200 mg per day.

The patient develops sexual dysfunction and reduced libido on sertraline. How would you manage this?

Reduced libido and sexual dysfunction are side effects of all SSRIs and dual action drugs (SNRI). Sexual dysfunction can be managed by adding a phosphodiesterase inhibitor-5 inhibitor (PDE-5 inhibitor) such as sildenafil (Viagra®). Reduced libido is harder to treat, but sometimes adding bupropion (Wellbutrin®) can help increase libido. Sometimes these side effects disappear without intervention.

The patient is switched to venlafaxine and sexual dysfunction and reduced libido continues to be a problem despite trials with sildenafil and bupropion. What are your options now?

Buspirone should be considered to replace the venlafaxine, as it is helpful in GAD and it has no sexual side effects. Vilazadone (Viibryd®), which is a newer drug, although not approved for anxiety disorders can be used off-label. So far, it seems to have fewer sexual side effects than pure SSRIs, so this would represent another option.

What role do you see for benzodiazepine therapy?

Benzodiazepines are extremely useful for acute periods of intense anxiety. They are contraindicated in patients with a substance abuse problem. They do provide immediate relief, and so if the patient understands that these drugs are to be used when all behavioral interventions fail, then benzodiazepines are an important piece of the management. Small amounts of benzodiazepines should be given, without refills, to drive the point home that these drugs are for emergencies only. If the patient runs out of benzodiazepines, they need to schedule a visit before the next refill, as their symptoms need to be re-evaluated.

All benzodiazepines have an onset of action of ten minutes after swallowing and hence the immediacy of the benefit serves anxious patients well. The difference amongst the benzodiazepines have to do with their half-lives. Longer half-life benzodiazepines, such as diazepam (Valium®), with a 20-100 hour half-life, offers the advantage that patients do not have to keep taking pills to feel better. On the other hand, the associated drowsiness and impaired cognitive functioning can be hazardous. Short half-life benzodiazepines such as lorazepam (Ativan®) or alprazolam (Xanax®) with half-lives of 10-20 hours are good for helping someone through a difficult situation, but allowing them to regain cognitive function fairly quickly. Alprazolam, for reasons which are not clear, tends to wear off with a resulting craving, whereas lorazepam does not have this issue, so the latter is superior to the former in that way. Clonazepam (Klonopin®) has the most ideal half-life (18-50 hours) in that this is usually the period of time in which the patient gets through his anxiety without needing another dose. As a result, clonazepam 0.5 mg prn anxiety, dispensing 15 pills, is my “go-to” prescription for people in distress who do not have substance abuse issues or tendencies.