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.
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, 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 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.
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…
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.
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 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 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.
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.
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.