Shirah Vollmer, MD

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.

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

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.

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. 

  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

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.

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. 

 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.

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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. 

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

You see a 26-year-old woman who has suffered recurrent episodes of chest pain and palpitations over the past 4 weeks, which have caused her to grow increasingly fearful of going out in public alone. The patient’s attacks begin with her suddenly getting scared and are followed by the rapid development of chest pain, palpitations, and a sense of feeling smothered.

The most recent attack occurred 4 days ago while she was in a shopping mall. It was so severe that her friends took her to an emergency room when she told them she thought she was going to die. The emergency room physician ordered several tests, including an electrocardiogram, and told her she had hyperventilated.

The most likely diagnosis is panic disorder. After a cardiac disorder has been excluded, the reasonable conclusion is that she is having recurrent panic attacks, which yields a diagnosis of panic disorder. She does not have agoraphobia, because although she is fearful about going out in public alone, she still manages to do that.

To say that she hyperventilated is not quite accurate, as it is important to convey to this young woman that she does have a medical diagnosis, though it is not cardiac in origin. Anxiety disorders are second only to disorders involving substance abuse as the most common psychiatric conditions in the United States.   

Are panic attacks synonymous with panic disorder?

No, a panic attack is like a headache in that it is a cluster of symptoms. When panic attacks occur on a regular basis and the person becomes preoccupied with having a panic attack, then a panic disorder is diagnosed.

More specifically, to quote the DSM-5, “the essential feature of panic disorder is the presence of recurrent, unexpected panic attacks followed by at least one month of persistent concern about having another panic attack, worry about the possible implications or consequences of the panic attacks, or a significant behavioral change related to the attacks.” In other words, panic attacks are common, but by themselves, they are not a disorder. When the attacks become the focal point of one’s mental life — when there is significant time and energy concerned about the next panic attack &mdash; then the diagnosis of panic disorder is appropriate. 

What other diagnoses might be considered, and what diagnostic tests should be done?

Very rarely, a pheochromocytoma can present with panic attacks. Loss, or unresolved grief, is often a contributing factor to the panic attack, so the physician should probe for recent changes. The “why now” question is critical. Since she also complains of feeling smothered, a pulmonary workup might also be a consideration.

In terms of psychiatric diagnosis, one might consider a personality disorder. Cluster B personalities tend to tilt towards dramatic presentations, and as such, one must consider whether this patient’s symptoms are in the context of other unstable behaviors. Depression is often comorbid with panic disorder, and so a thorough evaluation of her mood is mandated. It is also essential to rule out bipolar disorder, as she is at an age when panic attacks could be the first manifestation of a manic episode. Bipolar disorder is an important diagnosis not to miss, since prescribing her a selective serotonin re-uptake inhibitor (SSRI) without a mood stabilizer could exacerbate her manic symptoms.

Post-traumatic stress disorder (PTSD) might also be considered, as it is conceivable that she is being triggered by memories of painful experiences, and if her traumatic past is bubbling up, then this requires a different management program. Social anxiety would also be a consideration if her symptoms are precipitated when faced with meeting new people or people she is not very comfortable with. Substance abuse might also be considered, as it is important to determine that her symptoms are not related to detoxification.

As with all menstruating women, it would also be important to determine if her symptoms are related to her menstrual cycle and components of a premenstrual dysphoric disorder (PMDD) syndrome. Finally, given her age, a pregnancy test would also seem prudent.

What treatment options are available for managing panic disorder?

There are both pharmacological and non-pharmacological interventions. Pharmacologically, SSRIs are commonly prescribed, as are dual serotonin-norepinephrine reuptake inhibitors (SNRIs), such as venlafaxine. Either of these 2 classes of agents is indicated when there is significant impairment in daily functioning. These agents should be given for one year, or 6 months after symptoms have subsided.

For cases that are refractory to these interventions, mood stabilizers and/or atypical antipsychotics can be considered. These agents are ordinarily prescribed by a psychiatrist, and would be a possible indication for referral.

Non-pharmacologically, cognitive behavior therapy (CBT) and mindfulness-based stress reduction can both be useful. Promoting a healthy lifestyle with a good diet, withholding caffeine, and engaging in exercise will also help. As with all mental health-related diagnoses, stressing good sleep and hygiene is an essential part of the management program.

At what dose would you initiate the SSRI and how would you titrate it?

This is a critical question. People with panic disorder are very sensitive to medications, and as such, the starting dose needs to be very low. For example, if I were to start citalopram, I would start off with a 5 mg dose. A good rule of thumb is to initiate therapy with one-half of the lowest dose available for the SSRI agent selected. The dose should then be titrated to efficacy.

The physician needs to titrate the dose slowly, yet aggressively, until the symptoms abate. Clinically, this means adjusting the dose every 1-2 weeks until the patient is no longer concerned about having a panic attack. There is no need to push the dose higher once the symptoms have subsided.

The question often arises as to which SSRI or SNRI you should pick. One of the best ways to make this decision is either past history or biological family history of treatment response. If this information is not available, then a more sedating SSRI is a good place to start. Sertraline is often a wise choice for panic disorder patients, as it tends to be calming without being sedating or activating. However, sertraline is prone to cause mild gastrointestinal (GI) instability, so the patient needs to be warned about this.

What other side effects do you consider? 

All SSRIs and SNRIs can cause a discontinuation syndrome, with venlafaxine and paroxetine being the biggest offenders. As such, a slow taper is mandatory at the end of treatment.

Suicidal ideation must also be monitored during treatment. Anxiety is a known risk factor for suicide, and there is concern that SSRIs and SNRIs might increase suicide risk. As such, at every visit, the physician should inquire about both active and passive suicidal ideation.

Finally, SSRIs and SNRIs can inhibit libido and make it difficult to achieve an orgasm. Therefore, a sexual history should be part of every evaluation, with continual monitoring throughout treatment. 

Is there a role for benzodiazepine therapy in patients with panic disorder?

Absolutely. I tell my students there are 2 kinds of physicians: those who overprescribe benzodiazepines and those who underprescribe them. These drugs will abort a panic attack, and if used properly, they may prevent the person from developing a panic disorder.

Benzodiazepines can be very useful, provided the patient is not a substance abuser. The patient needs to be advised that in order to abort the symptoms, benzodiazepines need to be taken before the panic attack peaks. Benzodiazepines can reduce vigilance and eliminate muscle tension, but do not prevent worrying.

The key is that the patient needs to understand benzodiazepines can be used if and when needed. Having said that, they should be used judiciously, and as such, a limited quantity with limited refills should be prescribed. Use of benzodiazepines in therapeutic dosages does not generally lead to abuse and addiction. However, if the patient has a history of a substance abuse problem or a personality disorder, then benzodiazepines should be avoided.

In patients with panic disorder, prescribing a benzodiazepine often serves to relieve anxiety, even if the patient hardly uses it. I call these folks “Ativan in the purse” people because knowing that they have an antidote available often relieves their anxiety without having to use it. Consequently, there are many patients who carry the original prescription bottle first prescribed with them at all times, for years.

How long should this patient continue pharmacologic therapy?

Pharmacotherapy should be continued for one year. Typically, a patient becomes asymptomatic after 6 months, and then another 6 months of pharmacotherapy is necessary to prevent a relapse. The longer the person goes through life without panic attacks, the more likely it is that the patient will not have panic attacks in the future. This means that compliance is extremely important, as it is challenging to get a patient to take a medication after symptoms resolve.

It is helpful if the physician tells the patient that the treatment of panic disorder lasts at least a year, in order to prepare the patient for the long haul of intervention. This initial conversation sets the “contract” and hence will improve compliance as symptoms abate. Most patients with panic disorder will be treated in primary care, although indications for referral to a psychiatrist include suicidal ideation, comorbid substance abuse, and refractory to first- and second-line interventions.

Can you elaborate further on useful non-pharmacologic measures?

Typically, panic attacks come on after a loss, and so, psychotherapy is useful to determine the “why now” question. CBT is useful in helping the patient gain coping skills, which will abort the panic attack. For example, deep breathing exercises can stop the attack. Mindfulness-based stress reduction is another option among non-pharmacological measures for panic disorder.

Non-pharmacological measures share a common theme that patients can utilize in their pre-frontal cortex to control their oncoming symptoms. Helping the patient harness this higher level of thinking and understand that symptoms are non-lethal and merely indicate a symptom of stress can prevent the panic attack and redirect them to explore their inner world.

Further, helping patients understand that their symptoms are the result of excessive physiological arousal, and not an indication of impending demise, will often calm them. Likewise, teaching them that their symptoms are giving them cognitive distortions and that the symptoms are a result of poor coping skills will also help them seek out better ways of dealing with their internal disruptions.

Shirah Vollmer, MD, is Associate Clinical Professor of Psychiatry and Biobehavioral Sciences at the David Geffen School of Medicine at UCLA and a board-certified adult and child psychiatrist. All questions were posed by 

Panic attacks are common, but by themselves, they are not a disorder. When the attacks become the focal point of one's mental life, then the diagnosis of panic disorder is appropriate. 

Shirah Vollmer, MD

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