Anxiety Overview

Anxiety is a common problem for the people we see at Gateway Psychiatric, and some variation of request above is one of the most frequent questions people ask and yet it is also one of the most complicated to answer. It is puzzle. Patients feel anxiety in their bodies, so they naturally expect that a physical treatment like a medication will help. But anxiety disorders respond to our medications much less than other conditions.

Anxiety comes in many forms and means different things to different people. For example, it is common to hear someone say that they’re not anxious but they do worry a lot. To complicate things more, dread and hopelessness, which is one of the most common manifestations of depression, can also be confused with excessive anxiety.

So let’s begin by describing some of the types of anxiety that people experience.

Types of Anxiety

These are the most common types of anxiety that we see:

1. PTSD or Traumatic Anxiety: Intrusive fear or anxiety related to a traumatic event. There are often flashbacks, intrusive memories, or nightmares along with other symptoms.

2. Panic or Sudden Extreme Anxiety: Sudden overwhelming anxiety. Often associated with feeling as though you are going to die or go crazy.

3. Generalized Anxiety or Ongoing Worry about Many Things: Worrying about many different things over a long period of time.

4. Obsessional Anxiety or Recurring Worries: Worrying about one thing over and over.

5. Fearfulness or Paranoia: Fear that perhaps all is not as it seems, that perhaps people cannot be trusted.

6. Phobias: Anxiety linked to specific situations.

7. Agitated Anxiety and Racing Thoughts: Anxiety can also be a manifestation of what is called a “mixed state” and distinguishing this from other kinds of anxiety is both extremely important and very difficult.

MORE INFORMATION

PTSD or Traumatic Anxiety

Many people with mood disorders have experienced a traumatic event, which, as defined by the diagnostic manual for psychiatry, means “direct personal experience of an event that involves actual or threatened death or serious injury, or other threat to one’s physical integrity; or witnessing an event that involves death, injury, or a threat to the physical integrity of another person; or learning about unexpected or violent death, serious harm, or threat of death or injury experienced by a family member or other close associate.”

Common examples in our experience are: experiencing something as a child that felt like a threat to life, a sexual assault, experiencing other forms of violence.

These traumatic events seem to create the conditions for mood instability, and addressing them and their consequences in treatment is important for good recovery.

Panic or Sudden Extreme Anxiety

The most common form of this type of anxiety is a “panic attack”. Again, the diagnostic manual defines a panic attack as:

“intense fear or discomfort in the absence of real danger that is accompanied by many of the following physical or thought symptoms. Symptoms can include: palpitations, sweating, trembling or shaking, sensations of shortness of breath or smothering, feeling of choking, chest pain or discomfort, nausea or abdominal distress, dizziness or lightheadedness, feeling that suddenly things aren’t real or feeling disconnected from your self, fear of losing control or “going crazy,” fear of dying, funny tingling sensations in the body, and chills or hot flushes. The attack has a sudden onset and builds to a peak rapidly (usually in 10 minutes or less) and is often accompanied by a sense of imminent danger or impending doom and an urge to escape.”

Generalized Anxiety or Ongoing Worry about Many Things

This kind of worry, called “Generalized Anxiety” in the diagnosis manual, is very common among those with mood disorders, and is often the first “symptom” to develop, very commonly present in childhood. However, because it is chronic, many people don’t recognize it as something worth noting.

Here again is a description:

“The person finds it difficult to keep worrisome thoughts from interfering with attention to tasks at hand and has difficulty stopping the worry. Adults with Generalized Anxiety Disorder often worry about everyday, routine life circumstances such as possible job responsibilities, finances, the health of family members, misfortune to their children, or minor matters (such as household chores, car repairs, or being late for appointments). Children with Generalized Anxiety Disorder tend to worry excessively about their competence or the quality of their performance.”

Obsessional Anxiety or Recurring Worries

Some people tend to worry over and over again about specific worries. There are many types of worries, but the key to this type of worry is that the worry is intrusive and disturbing and is difficult to control. It may be about:

• Cleanliness, germs
• Neatness, order
• Forgetting to lock a door or turn off an electrical appliance
• Appearance
• Being overweight
• Or many other types of things.

This type of worry seems to be particularly responsive to a specific type of psychotherapy: behavioral therapy, and a particular type of medication: agents that enhance serotonin in the brain.

Fearfulness or Paranoia

Agitation and Racing Thoughts in Energized States

Often when someone is in an energized state there is a sense of “agitation” or needing to move as well as the experience that thoughts are “racing” or difficult to keep up with. Both of these experiences can happen with anxiety. Also, energized states that are associated with agitation are often not at all pleasant (not the happy state that people associate with being “manic”). In fact, despite the increased energy, they are often experienced as depressed states. The key to identifying this type of agitation is:

• Getting a lot done, or needing less sleep
• The racing thoughts are not about one thing, and they are not about familiar “worries”, they still have the quality of novelty that accompanies more typical hypomania.

Agitation in Depression

There is considerable controversy about agitated depression. Some people feel it doesn’t exist. Certainly it is very difficult to distinguish from anxiety and depression. In fact, the “agitation” and “racing thought” in this kind of depression is similar to the “recurrent anxiety” described above. It tends to be about one or more worries that recur over and over again. And if there is physical activity, it also tends to be repetitive: pacing up and down, wringing hands, etcetera.

Relationship between Anxiety and Other Mood Symptoms

in addition to various means of anxiety another important issue that has to be explored before making any recommendations for treating anxiety is the relationship between this symptom and other mood symptoms.

For some people there is no relationship between depressive symptoms or other mood symptoms and anxiety. In our experience this is most common for people who have generalized anxiety and discrete episodes of depression. Often the generalized anxiety shows up first, with many symptoms of worry present even in early childhood, and then discrete episodes of depression beginning in late adolescence or early adulthood.

For other people anxiety and mood symptoms tend to occur at the same time, or in a recurring pattern or sequence. Perhaps the first symptom of an episode of depression might be an increase in anxiety, or anxiety may show up in conjunction with moderate depression but disappear as the depression becomes more severe and lethargic. The importance of this kind of pattern is that it suggests that adequate treatment of mood symptoms should resolve the anxiety.

Treatment of Anxiety

Given the complexity of the various types of anxiety and the relationships between anxiety and mood symptoms, it may not be too surprising that the question of how best to treat anxiety is one of the most challenging questions we face in the practice.

A key issue to consider is that avoidance of anxiety or the things that provoke anxiety is often a very bad long-term strategy. Whereas in the short run it may make sense to try not to experience anxiety, for many people, doing this over time leads to more and more restricted lives. For this reason we pay particular attention to certain kinds of statements…

“I have to get rid of my anxiety…”

“I just can’t…”

These suggest that someone has unrealistic goals for coping with anxiety. All of us experience anxiety every day and any attempt to get rid of that anxiety is likely to be self-defeating.

Because avoidance is such an important problem we usually argue that the treatment of anxiety needs to begin with psychotherapy and medications should be considered as an adjunct to psychotherapy rather than as the primary modality of treatment. And psychotherapy needs to focus on teaching effective strategies for dealing with avoidance.

For most of the patients we see treatment of depressive symptoms and other mood symptoms with medications plus psychotherapy is the most effective combination. For some people there may be a role for medications for treating anxiety.

Benzodiazepines

Probably no topic in the field of psychiatry is more complicated and controversial than the role of benzodiazepines in the treatment of anxiety, and particularly in the treatment of chronic anxiety.

Some psychiatrists argue that there is no role for chronic treatment with benzodiazepines, others feel that, for all of their flaws, these medications may be helpful in selected patients with chronic anxiety.

One of the key issues in using benzodiazepines is that they are easily used as part of a pattern of avoidance that is harmful. If, when I feel anxious, I take a medication to get rid of that anxiety, and I don’t act to deal with the sources of that anxiety, the result can be a very restricted life. We have seen people who are essentially unable to function because they have become so enmeshed in this pattern of using medications to numb anxiety.

This can be especially problematic if benzodiazepines are combined with alcohol or other medications that have a similar numbing effect.

In general, we restrict the use of benzodiazepines to situations where there is a short term need to treat increased anxiety. For example, s stressor that is causing increased anxiety but is not likely to last.

For more information on benzodiazepines…

Antidepressants

Antidepressants, particularly serotonin antidepressants (SSRI’s and SNRI’s – see below), are the most common medications used to treat generalized anxiety, PTSD, obsessional anxiety and panic anxiety.

They can be quite effective, although, in our work with people with anxiety and mood symptoms, we find there is a very large range of effective doses. Some people respond to tiny doses and others requiring doses well above the normal therapeutic range.

Also, anxiety symptoms treated with antidepressants tend to gradually improve over an extended period of time. For that reason, a trial of one of these medications can take months.

As with their use in the treatment of depression, there is evidence that the SNRI’s, particularly venlafaxine, may be somewhat more effective than the SSRI’s, although with more potential for side effects.

For more information about antidepressants.

Buspirone

Buspirone has been repeatedly shown to be as effective in managing chronic generalized anxiety is benzodiazepines and almost as effective as serotonin antidepressants and yet it is medication that is rarely prescribed and when we do use it hard to convince people that it is really working.

For one thing, people who have been treated for a long time with benzodiazepines appear to be less likely to respond to buspirone. And buspirone does not cause sedation, which many people associate with effective anti-anxiety medication.

Finally, buspirone has a very gradual onset, since anxiety levels naturally vary from day to day, and even hour to hour, noticing a gradual reduction can be very difficult.

Off Label Medications

This is essentially the list of medications that have been approved in the treatment of anxiety. The remainder of this list consists of medications that are used “off label” to treat anxiety.

Gabapentin and Pregabalin

These medications which were initially developed as anticonvulsants and are often prescribed for chronic pain and fibromyalgia, can be helpful for some people with generalized anxiety. Unfortunately, they may have mood destabilizing effects and so should be used with caution in anyone with a bipolar spectrum depression. Pregabalin has more data supporting its effectiveness.

Atypical Antipsychotics

In some areas of the country these medications have replaced benzodiazepines as sedating agents used for the treatment of anxiety states, especially when prescribed by primary care doctors. This is worrisome given the significant long-term side effects, which are in some ways worse than the long-term side effects of benzodiazepines.

In our practice we tend to prescribe them either as adjuncts to medications being used to treat depression or bipolar, or as primary medications for treating fearfulness and paranoia.

However, for treatment resistant anxiety, they can be very effective. In particular, quetiapine (Seroquel) at doses of 100-200 mg at night may be especially helpful, either as monotherapy or as an adjunct to an antidepressant. As with the antidepressants, however, you have to give it a few weeks to work, immediate responses to the medication do not predict longer term effectiveness.

For more information…

Antihistamines

Medications like hydroxyzine and diphenhydramine are sedating antihistamines that may help some people with generalized anxiety. Since these medications have significant anticholinergic effects they should be used with caution in older patients. Hydroxyzine is more likely to be effective, in fact it is FDA approved for “relief of anxiety and tension associated with psychoneurosis,” which is probably something like what we now call generalized anxiety.

Beta Blockers

States of anxiety are often associated with activation of the sympathetic nervous system. Norepinephrine and epinephrine in the body activate beta receptors and alpha receptors. Thus, medications to block these effects are either beta blockers or alpha blockers.

Propranolol is probably the medication most often prescribed for performance anxiety and social anxiety. It is most helpful for treating the physical manifestations of high anxiety such as tremor, racing heart, and to a lesser extent flushing and sweating.

Other Adrenergic Agents

CLONIDINE

Clonidine is an alpha-2 adrenergic agonist or stimulator. Alpha-2 receptors counteract the effects of the activated sympathetic nervous system. Clonidine is primarily used to treat hypertension and withdrawal from opiates. It counteracts some of the physical symptoms associated with states of high sympathetic nervous system activation. It has to be managed carefully as it can be associated with significant symptoms if too much is taken or if it is stopped suddenly.

PRAZOSIN

Prazosin is an alpha-1 blocker that is primary used to treat sleep disruption due to activation of the sympathetic nervous system, especially nightmares in PTSD.

Natural Supplements

Silexan

Although the research on this natural agent was primarily done in Europe, and was mostly sponsored by the manufacturer, it has probably some of the best evidence to support its effectiveness in generalized anxiety of any natural supplement.

Silexan is a branded extract of lavender that was developed by Schwabe Pharmaceuticals in 2002. Its active ingredients—linalool and linalyl acetate—comprise 71% of the oil, with the remaining 29% made up of trace amounts of over a hundred other compounds from the lavender plant. Silexan is regulated as a prescription and licensed for anxiety in 14 countries. In the US, it is available over the counter as CalmAid, through Schwabe’s “Nature’s Way” line.

Silexan’s pharmacologic properties are more in line with conventional medications than with most natural supplements. It inhibits calcium channels (like pregabalin), it has GABA-ergic effects (as do the benzodiazepines), it is an NMDA antagonist (one of ketamine’s actions); and like buspirone and vortioxetine, it is a serotonin-1A agonist. The serotonin-1A agonism is probably the most relevant mechanism, judging from animal studies where Silexan’s anxiolytic effects were measured after blocking the various mechanisms (Baldinger P et al, Int J Neuropsychopharmacol 2014;18(4):pyu063).

Doses of 80 mg and 160 mg have been shown to be effective, with a slightly larger effect size at the higher dose.

Other Natural Supplements

A network meta-analysis of a number of other supplements for the treatment of anxiety disorders and anxiety found that “Medicinal herbs may be promising for the treatment of anxiety. However, these results should be considered preliminary because of the unconvincing sample sizes, together with the potential effectiveness of placebos.” In other words, there is not good data supporting their effectiveness.

References

Aljuhani, Turky. “Pharmaceutical Management of General Anxiety Disorder.” Journal of Pharmaceutical Research International 33 (2021): 395–405. Web.

Baldinger P, Höflich AS, Mitterhauser M, Hahn A, Rami-Mark C, Spies M, Wadsak W, Lanzenberger R, Kasper S. Effects of Silexan on the serotonin-1A receptor and microstructure of the human brain: a randomized, placebo-controlled, double-blind, cross-over study with molecular and structural neuroimaging. Int J Neuropsychopharmacol. 2014 Oct 31;18(4):pyu063. doi: 10.1093/ijnp/pyu063. PMID: 25522403; PMCID: PMC4360214.

Baldwin, D. “Recent Guidelines for Evidence-Based Pharmacological Treatment of Social Anxiety Disorder.” European psychiatry 33.S1 (2016): S46–S47. Web.

Kasper, Siegfried et al. “Lavender Oil Preparation Silexan Is Effective in Generalized Anxiety Disorder – a Randomized, Double-Blind Comparison to Placebo and Paroxetine.” The international journal of neuropsychopharmacology 17.6 (2014): 859–869. Web.

Martin, Alicia et al. “Treatment Guidelines for PTSD: A Systematic Review.” Journal of clinical medicine 10.18 (2021): 4175–. Web.

Stein, Murray B, and Jitender Sareen. “Generalized Anxiety Disorder.” The New England journal of medicine 373.21 (2015): 2059–2068. Web.

Zhang, Wenting et al. “Medicinal Herbs for the Treatment of Anxiety: A Systematic Review and Network Meta-Analysis.” Pharmacological research 179 (2022): 106204–106204. Web.

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