AbstractAnxiety disorders are among the most common primary care challenges in a women’s health practice. A comprehensive approach includes identifying the symptoms, characterizing the disorder, and evaluating whether the patient has a medical condition such as hyperthyroid, substance abuse, supraventricular tachycardia, or asthma that manifests as anxiety. Conventional treatments for generalized anxiety disorder and panic disorder include a range of antidepressants, sedatives, benzodiazepines, and cognitive therapy. Evidence-based nutraceuticals and botanicals include GABA, L-theanine, passion flower, skullcap, hops, kava, and lavender oil.
Anxiety in Women
Anxiety disorders, the most common psychiatric disorder in women, are at least twice as common in women as in men.1 Women suffer from a variety of anxiety disorders, with the most common being generalized anxiety disorder (GAD), panic disorder, posttraumatic stress disorder (PTSD), obsessive-compulsive disorder (OCD), social phobia, and specific phobia.
Generalized Anxiety Disorder
GAD is experienced as excessive anxiety and worry that a woman finds difficult to control. To qualify as GAD, these symptoms must be present for more days than not, persist for at least 6 months, and not meet the criteria for the diagnosis of another anxiety disorder. In women, GAD has a lifetime prevalence of 6.6% with a 1-year prevalence of 4.3%. Generalized anxiety symptoms may also worsen in women in the premenstrual phase, in the post-childbirth phase, and in the perimenopause transition. Women with generalized anxiety disorders are also more likely than men to have coexisting psychiatric disorders.2
Panic disorder is twice as common in women as in men, and women are also twice as likely as men to have panic with agoraphobia.3 Signs and symptoms of a panic attack may include palpitations, sweating, trembling, shortness of breath, choking, chest pain, nausea or sudden gastrointestinal symptoms, dizziness or lightheadedness, derealization, fear of losing control, fear of dying, paresthesias, chills, and flushing. A patient must have at least 4 of these signs and symptoms for a diagnosis of panic disorder. Symptoms occur abruptly and reach a peak within 10 minutes. Limited research exists about panic disorders during pregnancy and postpartum; however, some small studies and case reports have found that panic symptoms appear to improve during pregnancy. This finding lacks confirmation with larger studies. Panic symptoms worsened in the postpartum period in some small studies, but results have been inconsistent.4–6
Women are more likely than men to relapse after experiencing remission of their panic and anxiety symptoms.7
Post-traumatic Stress Disorder (PTSD)
The most common traumas contributing to PTSD in women are rape and sexual molestation.8
Unlike many other anxiety disorders, obsessive-compulsive disorder (OCD) is equally common in women and men, although women tend to develop it later in life, have more coexisting depression, and experience more severe symptoms than do men.9 Lastly, women are about twice as likely as men to have social phobias and specific phobias, although men are more likely to seek treatment.10
Before concluding that an anxiety disorder is the cause of a patient’s symptoms, it is important to rule out other medical illnesses and conditions that may manifest as anxiety. No laboratory tests or imaging studies can confirm a diagnosis of an anxiety disorder; therefore clinical judgment and a careful clinical history are the only means to distinguishing an anxiety disorder from other issues that may mimic or coexist with it.
Symptoms that may require urgent evaluation include chest pain, choking, dizziness, shortness of breath, palpitations, and numbness and tingling sensations, which could be signs of a serious medical condition. Examples of medical conditions that produce anxiety or anxiety-like symptoms include substance-induced disorders, cardiac disorders (eg, arrhythmia, myocardial infarction), pulmonary conditions (eg, asthma), and endocrine disorders (eg, hyperthyroidism, perimenopause and menopause, premenstrual syndrome, high or low blood sugar).
Guideline to differential diagnosis:
Substance-induced or medical causes of anxiety are more likely if
- first presentation of symptoms is after the age of 40,
- there is a fluctuation in the level of consciousness, or
- evidence of autonomic instability exists.
Anxiety is more likely if
- the patient is concerned about losing control in her life,
- the patient has a family history of anxiety issues,
- symptoms present between the ages of 18 and 45, or
- the patient has a recent or anticipated stressful event or has agoraphobia.
A comprehensive substance abuse history and medication/supplement history is important in evaluating a patient for anxiety. This includes over-the-counter, prescription, alcohol or recreational drug use, appetite suppressants, herbs, nutrients, nicotine, and caffeinated beverages.
Withdrawal from substances, including alcohol, nicotine, caffeine, opiates, or benzodiazepines, should also be considered as a cause of symptoms. Short-acting benzodiazepines such as alprazolam may cause withdrawal symptoms between doses. Caffeinism symptoms (ie, diuresis, insomnia, anxiety, withdrawal headache, diarrhea, tachycardia, remulous) are similar to symptoms of anxiety disorders.
Women with anxiety disorders often have substance abuse issues as well, maybe even as a result of medicating their anxiety disorder. In one study, women with alcohol abuse problems were 2 to 3 times more likely have depression or an anxiety disorder compared to other women.11 In another related study on this subject, women with cocaine dependence had anxiety disorders at twice the rate as did men with cocaine dependence.12
Several cardiac issues have clinical similarities to panic disorder. Women with supraventricular tachycardia (SVT) are about twice as likely as men to also have the diagnosis of panic or anxiety, which is often a reason SVT does not get diagnosed properly.13 This is a good illustration of the importance of considering SVT in individuals with anxiety symptoms. Other cardiac problems also may present with anxiety symptoms, including myocardial infarction, mitral valve prolapse, coronary insufficiency, congestive heart failure, and anemia.
Although it is usually possible for the clinician to distinguish between acute asthma and a panic attack, the two events can share many of the same symptoms (eg, dyspnea, chest tightness). It can also be difficult to diagnose an anxiety disorder in a patient who has known asthma or chronic obstructive pulmonary disease because panic is more common in these patients when they have dyspnea. This may lead to overuse of their rescue inhalers and corticosteroids, as well as an increase in hospital admissions.
Hyperthyroidism is a well-known mimic of anxiety disorders with symptoms such as tachycardia, perspiration, jittery feelings, and more. Hyperthyroidism is 10 times more common in women men than in men and is most prevalent between ages 30 and 40.14 Hyperthyroidism is also a potential issue during pregnancy and can be worse postpartum.15 The incidence of hyperthyroidism during pregnancy is 1 in 500.15 Onset or worsening of anxiety during postpartum should instigate thyroid testing.
Symptoms associated with perimenopause and menopause, such as insomnia, irritability, and fatigue, can also be confused with an anxiety disorder. On the other hand, anxiety and panic disorder can be initiated or worsened during the perimenopausal transition due to hormonal fluctuations.
Endocrinology issues that run the risk of being diagnosed as an anxiety disorder and escape proper diagnosis include pheochromocytoma, congenital adrenal hyperplasia, hypoglycemia, the hypercalcemia or hypocalcemia associated with abnormal parathyroid function, Addison’s disease, Cushing’s syndrome, and carcinoid syndrome.
Conventional treatment for GAD tends to focus on venlafaxine or buspirone. Other options include paroxetine, tricyclic antidepressants, and trazodone. Benzodiazepines are also effective, especially for acute symptoms, but can be more difficult to manage in the initial treatment phase. Cognitive behavior therapy (CBT) and cognitive therapy are also helpful, but medications provide benefits that last over time.16 CBT is also an important intervention: One study showed that 88% of patients who received CBT were panic-free after one year.17
Panic disorders are definitely more difficult to treat. This is due in part to patients’ suspicion and fear of side effects and increased somatic sensitivities. Paroxetine, sertraline, fluoxetine, fluvoxamine, imipramine, and clomipramine have all been shown to be more effective than placebo in clinical trials.18–22 Benzodiazepines are also used for panic disorder, but the potential for dependence and withdrawal make them less appealing for long-term use. A benzodiazepine with a longer half-life, such as clonazepam, is often a wiser choice than a shorter-acting medication with greater addiction possibility and dose-to-dose withdrawal problems.
Nutritional and botanical supplements
Fortunately, many excellent nutritional and botanical supplements can reduce the frequency, severity, and duration of generalized anxiety and panic disorders. It all starts with managing stress and optimizing lifestyle habits such as sleep, regular and healthy eating, regular exercise, and reduction of stimulants.
Gamma-aminobutyric acid (GABA)
The primary inhibitory neurotransmitter in the central nervous system, GABA is synthesized in the brain from the amino acid glutamate with the aid of vitamin B6. It exerts sedative and anxiolytic effects at the cellular level. Many of the conventional medications used to treat anxiety disorders work at least in part by enhancing GABA activity. While this supplement is popular among alternative practitioners, adequate clinical trials proving its efficacy are lacking.
The major amino acid in green tea, also found in some mushrooms, L-theanine has been used historically for its relaxing and antianxiety effects and is thought to work by increasing levels of GABA and serotonin. Evidence suggests that L-theanine can induce feelings of tranquility and calm.23
Passionflower (Passiflora incarnate)
Passionflower is used for insomnia, digestive upset related to anxiety or nervousness, GAD, and even symptoms of opiate withdrawal. Symptoms of anxiety, nervousness, tension, and heightened reactions to stress can occur especially in women during the premenstrual phase, perimenopause transition, and postpartum. A double-blind randomized trial comparing passionflower with a prescription anxiety medication found both treatments equally effective in the treatment of GAD.24 No significant difference was observed between the 2 treatments, but there were significantly fewer problems related to impairment of job performance with the passionflower.
Skullcap (Scutellaria lactiflora)
Skullcap has been used historically for insomnia, anxiety, as a nerve tonic and sedative for nervous tension and spasms. Its principle flavonoids found are baicalin and wogonin; it is thought that these and the other flavonoid constituents of skullcap might act as GABA agonists, therefore creating a sedating and anxiolytic effect.
Hops (Humulus lupulus)
Used as a preservative and flavoring agent in beer production, hops also helps ease tension, excitability, nervousness, irritability, restlessness, and sleep disorders. Only a few studies have been conducted on the sedating effects of hops, including 4 in combination products with valerian; thus we cannot separate the potential benefits of valerian in these studies, which leaves us unclear just how effective hops is.25–27
While hops contains many constituents, including flavonoids and bitter acids, it is the volatile oils of hops that have been associated with its sedative properties.28 In particular, the 2-methyl-3-butene-2-ol in the volatile fraction has been identified as a primary sedative and hypnotic constituent of hops.29
Kava (Piper methysticum)
Kava appears to have at least moderate efficacy in the treatment of anxiety. A systematic review (from the Cochrane data base) and meta-analysis of randomized controlled trials in 2000 found a significant overall reduction in anxiety symptoms with standardized extract of kava.30 In an update of this analysis in 2003, additional studies were added and again, there was a significant reduction in anxiety in patients receiving kava extract compared to placebo.30 There is quite a collection of other studies on kava in treating generalized anxiety, anxiety in postmenopausal women and perimenopausal women, and other anxiety states. Some studies look at using kava while tapering benzodiazepines, or using kava with hormone replacement therapy. Most, but not all, of these studies show efficacy in reducing anxiety.
The mechanism for the anxiolytic effect of kava is not clear. The research on its ability to modulate GABA receptors is conflicting; evidence suggests that kavalactones modulate GABA activity through lipid membrane structure and sodium channel function rather than by antagonism of the GABA receptors.31,32
Concern regarding the potential hepatotoxicity of kava with cases of liver damage have been well publicized. Most cases were not well-reported and involved coingestion of alcohol, excessive dosage, or inappropriate preparations of the plant, including aerial parts, root, or stem peelings, which are higher in the toxic alkaloids.33,34 General guidelines for safe use include using aqueous root preparations standardized for kavalactones and not exceeding 250 mg/day of those kavalactones. Kava should be avoided in known liver disease and not administered with alcohol.
Lavender (Lavandula angustifolia)
Lavender oil has also been shown to be effective when delivered orally. Several clinical studies have demonstrated the benefit of lavender extracts compared to study drug or placebo in decreasing anxiety and depression. Orally administered lavender capsules were tested in 1 randomized, double-blind, placebo-controlled trial.35 The authors concluded that lavender had anxiolytic effects under conditions of low anxiety, but they were unable to draw conclusions about high anxiety or clinical anxiety disorders.
Another study of lavender oil for anxiety disorder compared it to placebo. This was the first double-blind randomized clinical trial to document the anxiolytic efficacy of oral lavender essential oil for anxiety disorder.36 Researchers concluded that the lavender oil was both efficacious and safe and had a significant effect on reducing anxiety symptoms on several anxiety scales and also improved the quality and duration of sleep and improved general mental and physical health without sedation or drug-like side effects.
A multicenter, randomized trial was done comparing lavender oil to low-dose lorazepam in patients with GAD.37 The results demonstrated that the lavender oil capsules were comparable in results to the conventional study drug; the Hamilton Anxiety Rating Scale score decreased by 45% in the lavender group and by 46% in the drug group. By the end of the 6-week trial, it was a 40% decrease in the lavender group and 27% in the drug group. In addition, the response rate was 52.5% in the lavender oil group vs only 40.5% with the conventional treatment. Lavender oil capsules can elicit a lavender eructation, nausea, and dyspepsia in 2.6% to 5.2% of patients.
Some potential cautions are worth noting relative to the herbs and nutrients discussed here. Intravenous GABA has been known to cause dysphoria and dose-related increases in blood pressure. L-theanine may potentiate the activity of antihypertensive medications and may decrease the effects of stimulant drugs. Passionflower, skullcap, and hops could potentiate the actions of barbiturates, alcohol, and central nervous system depressant medications, including the sedative effects of antihistamines. Take caution in using hops in cases of depression. In pregnant or nursing women, each ingredient must be evaluated carefully for safety.
Anxiety disorder in perimenopausal women is common. In these patients, the most successful outcomes are achieved when the underlying hormonal influences are addressed. This may be accomplished with botanicals, nutritional supplements, and/or hormone management. It is important to assess the potential benefits of estrogen/progesterone in these women. Stabilizing brain chemistry, sleep cycles, and other menopause symptoms such as hot flashes can be vital to treating anxiety disorders. The key to success is using black cohosh, maca, another botanical menopause combination, and/or estrogen/progesterone as the foundation and then the particular anxiety symptom intervention in addition. This same concept is effective in women with premenstrual anxiety or premenstrual exacerbation of anxiety: Use a premenstrual syndrome treatment strategy and then add the anxiety specific treatment.
- Kessler R, McGonagle K, Zhao S, et al. Lifetime and 12-month prevalence of DSM-III-R psychiatric disorders in the United States: results from the National Comorbidity Survey. Arch Gen Psychiatry. 1994;51:8-19.
- Howell H, Brawman-Mintzer O, Monniewr J, Yonkers K. Generalized anxiety disorder in women. Psychiatr Clin North Am. 2001;24:165-178.
- Eaton W, Kessler R, Wittchen H, Magee W. Panic and panic disorder in the United States. Am J Psychiatry. 1994;151:413-420.
- Altshuler L, Hendrick V, Cohen L. Course of mood and anxiety disorders during pregnancy and the postpartum period. J Clin Psychiatry. 1998;59(suppl) 2):29-33.
- Cohen L, Sichel D, Faraone S, et al. Course of panic disorder during pregnancy and the puerperium: a preliminary study. Biol Psychiatry. 1996;39:950-954.
- Hertzberg T, Wahlbeck K. The impact of pregnancy and puerperium on panic disorder: a review. J Psychosom Obstet Gynaecol. 1999;20:59-64.
- Yonkers K, Zlotnick C, Allsworth J, et al. Is the course of panic disorder the same in women and men? Am J Psychiatry. 1998;155:596-602.
- Breslau N, Kessler R, Chilcoat H, et al. Trauma and posttraumatic stress disorder in the community: the 1996 Detroit Area Survey of Trauma. Arch Gen Psychiatry. 1998;55:626-632.
- Nestadt G, Bienvenu O, Cai G, et al. Incidence of obsessive-compulsive disorder in adults. J Nerv Ment Dis. 1998;186:401-406.
- Schneier F, Johnson J, Hornig C, et al. Social phobia. Comorbidity and morbidity in an epidemiologic sample. Arch Gen Psychiatry. 1992;49:282-288.
- Brady K, Randall C. Gender differences in substance use disorders. Psychiatr Clin North Am. 1999;22:241-252.
- Rounsaville B, Anton S, Carroll K, et al. Psychiatric diagnoses of treatment-seeking cocaine abusers. Arch Gen Psychiatry. 1991;48:43-51.
- Lessmeier T, Gamperling D, Johnson-Liddon V, et al. Unrecognized paroxysmal supraventricular tachycardia: potential for misdiagnosis as panic disorder. Arch Intern Med. 1997;157(5):537-543.
- Wallis L, ed. Textbook of Women’s Health. Philadelphia, PA: Lippincott-Raven;1998;527-528.
- Nuwayhid B, Khalife S. Medical complications of pregnancy. In: Hacker N, Moore J, eds. Essentials of Obstetrics and Gynecology. 2nd ed. Philadelphia, PA: WB Saunders Co;1992;208-209.
- Falsetti S, Davis J. The nonpharmacologic treatment of generalized anxiety disorder. Psychiatr Clin North Am. 2001; 24:99-117.
- Practice guideline for the treatment of patients with panic disorder. Work Group on Panic Disorder. American Psychiatric Association. Am J Psychiatry. 1998;155(5 supl):1-34.
- Louie A, Lewis T, Lannon R. Use of low-dose fluoxetine in major depression and panic disorder. J Clin Psychiatry. 1993;54:435-438.
- Oehrberg S, Christiansen P, Behnke K, et al. Paroxetine in the treatment of panic disorder: a randomised, double-blind, placebo-controlled study. Br J Psychiatry. 1995;167:374-379.
- Pohl R, Wolkow R, Clary C. Sertraline in the treatment of panic disorder: a double-blind multicenter trial. Am J Psychiatry. 1998;155:1189-1195.
- Hoehn-Saric R, McLeod D, Hipsley P. Effect of fluvoxamine on panic disorder. J Clin Psychopharmacol. 1993;13:321-326.
- Modigh K, Westberg P, Eriksson E. Superiority of clomipramine over imipramine in the treatment of panic disorder: a placebo-controlled trial. J Clin Psychopharmacol. 1992;12:251-261.
- Lu K, Gray M, Oliver C, et al. The acute effects of L-theanine in comparison with alprozolam on anticipatory anxiety in humans. Human Psychopharmacol Clin Exp. 2004;19:457-465.
- Akhondzadeh S, Naghavi HR, Vazirian M, et al. Passionflower in the treatment of generalized anxiety: a pilot double-blind randomized controlled trial with oxazepam. J Clin Pharm Ther. 2001;26:363-367.
- Schmitz M, Jackel M. Comparative study for assessing quality of life of patients with exogenous sleep disorders treated with a hops-valerian preparation and a benzodiazepine drug. Wien Med Wochenschr. 1998;148(13):291-298.
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- Hansel R, Wohlfart R, Coper H. Sedative-hypnotic compounds in the exhalation of hops, II. Z. Naturforsch. 1980;35 (11-12):1096-1097.
- Pittler M, Ernst E. Kava extract for treating anxiety. Cochrane Database Syst Rev. 2002;(2):CD003383.
- Yuan C, Dey L, Wang A, et al. Kavalactones and dihydrokavain modulate GABAergic activity in a rat gastric-brainstem preparation. Planta Med. 2002;68:1092-1096.
- Magura E, Kopanitsa M, Gleitz J, et al. Kava extract ingredients, (_)-methysticin and (+/-)-kavain inhibit voltage-operated Na (+)-channels in rat CA1 hippocampal neurons. Neuroscience. 1997;81:345-351.
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- Bradley BF, Brown SL, Chu S, Lea RW. Effects of orally administered lavender essential oil on responses to anxiety-provoking film clips. Hum Psychopharmacol. 2009;24(4):319-330.
- Kasper S, Gastpar M, Müller WE, et al. Silexan, an orally administered Lavandula oil preparation, is effective in the treatment of 'subsyndromal' anxiety disorder: a randomized, double-blind, placebo controlled trial. Int Clin Psychopharmacol. 2010;25:277-287.
- Woelk H, Schlaefke S. A multi-center, double-blind, randomised study of the Lavender oil preparation Silexan in comparison to Lorazepam for generalized anxiety disorder. Phytomedicine. 2010;17:94-99.