Phobic Disorders Medication
- Author: Adrian Preda, MD; Chief Editor: Iqbal Ahmed, MBBS, FRCPsych(UK) more...
Pharmacotherapy for phobic disorders (ie, social anxiety disorder, specific phobia, and agoraphobia) includes antidepressant agents (eg, selective serotonin reuptake inhibitors [SSRIs] and selective serotonin/norepinephrine reuptake inhibitors [SNRIs]), benzodiazepines, serotonin (5HT) 1 agonists, antihypertensive agents, tricyclic antidepressants (TCAs), and monoamine oxidase inhibitors (MAOIs).
SSRIs can help prevent panic attacks and alleviate symptoms of anxiety and depression. These drugs may require 2-6 weeks of daily use to become effective, usually with side effects appearing first. SSRIs have been shown to be effective in controlled clinical trials, and as a class, these medications tend to have the fewest adverse effects. However, the SSRIs can produce drug-drug interactions by inhibiting cytochrome P450 enzymes and by displacing other drugs from protein-binding sites.
SSRIs are greatly preferred to other classes of antidepressants for the treatment of anxiety disorders, and they all appear to be similarly efficacious. The choice of an SSRI depends on adverse effects, drug interactions, and history of previous response.
The relatively benign adverse effect profile of SSRIs (including minimal anticholinergic effects) facilitates compliance. Common adverse effects include insomnia, ejaculation disorder (primarily ejaculatory delay), nausea, sweating, fatigue, somnolence, and sexual dysfunction. SSRIs do not carry the cardiac arrhythmia risk associated with TCAs.
Citalopram enhances serotonin activity through selective reuptake inhibition at the neuronal membrane. This agent is not approved by the US Food and Drug Administration (FDA) for treatment of anxiety disorders, but data from randomized, controlled trials support its use for treatment of agoraphobia.
Escitalopram is an S-enantiomer of citalopram. The onset of depression relief may be obtained after 1-2 weeks, which is sooner than relief can be obtained with other antidepressants, suggesting that escitalopram may work faster than similar drugs.
Although this agent is not approved by the FDA for treatment of phobic disorders, its class membership and good tolerability make it an attractive option for long-term treatment. Off-label use of escitalopram for anxiety disorders includes social anxiety disorder (social phobia), panic disorder, and obsessive-compulsive disorder (OCD). Escitalopram is not approved for use in children younger than 12 years.
Paroxetine is a potent selective inhibitor of neuronal serotonin reuptake, but it has a weak effect on norepinephrine and dopamine neuronal reuptake. This agent is a low-affinity antagonist at some subtypes of muscarinic acetylcholine receptors and is a nitric oxide synthase inhibitor. The anticholinergic effects of paroxetine may result in sedation or cardiovascular effects.
Paroxetine is FDA-approved for use in social anxiety disorder (social phobia), panic disorder, generalized anxiety disorder, OCD, major depressive disorder (MDD), premenstrual dysphoric disorder (PMDD), and posttraumatic stress disorder (PTSD).
Sertraline selectively inhibits presynaptic serotonin reuptake and is a low-potency dopamine and norepinephrine reuptake inhibitor. It is-FDA approved for use in social anxiety disorder; panic disorder; major depressive disorder; OCD in adults, children, and adolescents; PMDD; and PTSD.
Fluoxetine selectively inhibits presynaptic serotonin reuptake but has minimal or no effect on reuptake of norepinephrine or dopamine. A common side effect is sexual dysfunction, which may impact long-term compliance. Fluoxetine is FDA-approved for use in panic disorder (with and without agoraphobia) and OCD, as well as other disorders.
Fluvoxamine enhances serotonin activity through selective reuptake inhibition at the neuronal membrane. Because this drug does not significantly bind to alpha-adrenergic, histamine, or cholinergic receptors, it has fewer side effects than TCAs do. Fluvoxamine is FDA-approved for treating OCD in children (8-17 years) and adults; it is also approved for treating social anxiety disorder. Fluvoxamine may be helpful for other anxiety disorders as well.
SNRIs can help prevent panic attacks and alleviate symptoms of anxiety and depression.
Venlafaxine is a reuptake inhibitor of both serotonin and norepinephrine. It is FDA-approved (in the extended-release capsule only) for the treatment of social phobia, panic disorder with or without agoraphobia, and generalized anxiety disorder.
In general, this category of medication should not be prescribed to patients with a history of alcohol/drug abuse or emotional dependence. Some psychiatrists feel that the longer-acting benzodiazepines (eg, diazepam, clonazepam) have advantages such as less frequent dosing and more consistent levels throughout the day. Slowly taper benzodiazepines (usually after 6 mo) to avoid withdrawal and to avoid precipitating panic.
Alprazolam is the best-studied benzodiazepine. It has a rapid onset (20 minutes) and a short half-life, which can contribute to increased dependency during tapering attempts. Alprazolam is FDA approved for use in panic disorder, with or without agoraphobia, generalized anxiety disorder, and anxiety disorders (in the immediate-release tablet).
Lorazepam is a sedative hypnotic with a short onset of effects and a relatively long half-life. By increasing the action of gamma aminobutyric acid (GABA), which is a major inhibitory neurotransmitter in the brain, lorazepam may depress all levels of the central nervous system (CNS), including the limbic and reticular formation. This agent is FDA-approved for use in anxiety disorders.
When a patient must be sedated for longer than 24 hours, lorazepam is an excellent choice. It is not significantly metabolized by the liver, and it can be administered either intravenously (IV) or intramuscularly (IM).
Clonazepam is a long-acting benzodiazepine that increases presynaptic GABA inhibition and reduces monosynaptic and polysynaptic reflexes. This drug also suppresses muscle contractions by facilitating inhibitory GABA neurotransmission and other inhibitory transmitters. Clonazepam reaches peak plasma concentration at 2-4 hours after oral or rectal administration.
Clonazepam has multiple indications, including suppression of myoclonic, akinetic, or petit mal seizure activity and focal or generalized dystonias (eg, tardive dystonia). This agent is FDA-approved for use in anxiety disorders.
Diazepam modulates the postsynaptic effects of GABA-A transmission, thereby bringing about an increase in presynaptic inhibition. This agent appears to act on part of the limbic system, the thalamus, and hypothalamus to induce a calming effect and has also been found to be an effective adjunct for the relief of skeletal muscle spasm caused by upper motor neuron disorders. This agent is FDA-approved for use in anxiety disorders.
Diazepam is rapidly distributed to other body fat stores. To avoid adverse effects, the diazepam dosage should be individualized and increased cautiously; the serum concentration of the drug drops to 20% of its peak value 20 minutes after the initial IV infusion.
Serotonin agonists such as buspirone may be used to treat anxiety.
Buspirone is an antianxiety agent that is not chemically or pharmacologically related to the benzodiazepines, barbiturates, or other sedative or anxiolytic drugs. Rather, it is a 5-HT1 agonist with serotonergic neurotransmission and some dopaminergic effects in the CNS. Buspirone has an anxiolytic effect but may take up to 2-3 weeks to reach its full efficacy. Buspirone is approved for the treatment of anxiety disorders or short-term relief of the symptoms of anxiety.
Antihypertensive agents are useful for the circumscribed treatment of situational/performance anxiety on an as-needed basis.
Beta-adrenergic blockers reduce the inotropic state of the left ventricle (LV), decrease diastolic dysfunction, and increase LV compliance, thereby reducing the pressure gradient across the LV outflow tract. Decreasing myocardial oxygen consumption reduces myocardial ischemia potential, and lowering the heart rate reduces myocardial oxygen consumption and myocardial ischemia potential.
Atenolol acts by selectively blocking beta1 receptors, with little or no effect on beta2 receptors. Beta-blockers affect blood pressure via multiple mechanisms, including a negative chronotropic effect that decreases heart rate at rest and after exercise, a negative inotropic effect that decreases cardiac output, reduction of sympathetic outflow from the CNS, and suppression of renin release from the kidneys.
Atenolol is used to improve and preserve hemodynamic status by acting on myocardial contractility, reducing congestion, and decreasing myocardial energy expenditure. During IV administration, the patient's blood pressure, heart rate, and electrocardiogram (ECG) must be carefully monitored.
Propranolol is recommended for situational social anxiety (stage fright) on an as-needed basis. An oral (PO) dose of 10-20 mg is given
The tricyclic antidepressants (TCAs) clomipramine and imipramine have demonstrated efficacy for the treatment of panic disorder with and without agoraphobia. These are also relatively inexpensive medications. However, due to their broad spectrum of action and their inhibition of multiple neurotransmitter systems, the TCAs have more side effects, such as anticholinergic and cardiovascular side effects, and therefore, these agents present problems for long-term treatment. The treatment response of TCAs occurs on the same order as the Selective serotonin reuptake inhibitors (SSRIs), within 2-6 weeks.
TCAs have a black box warning that states that patients with major depressive disorder (MDD), both adult and pediatric, may experience worsening of their depression and/or the emergence of suicidal ideation and behavior (suicidality) or unusual changes in behavior, whether or not they are taking antidepressant medications.
Clomipramine is a dibenzazepine compound that belongs to the TCA family. It acts by inhibiting the membrane pump mechanism responsible for norepinephrine and serotonin uptake in adrenergic and serotonergic neurons. Clomipramine affects serotonin uptake; it also affects norepinephrine uptake when converted into its metabolite desmethylclomipramine. Clomipramine acts as an antagonist at muscarinic acetylcholine receptors and is also an antagonist at histamine H1 receptors.
Clomipramine is approved by the FDA for use in the treatment of OCD (adult and pediatric, age ≥10 years).
Imipramine hydrochloride inhibits reuptake of norepinephrine or serotonin at the presynaptic neuron. This agent is an antagonist at histamine H1 and alpha1 adrenoceptors, as well as at M2 muscarinic acetylcholine receptors. Parenteral administration can be used for starting therapy only in patients unable or unwilling to use oral medication.
Antidepressants, MAO Inhibitors
MAOIs are most commonly prescribed for patients with social anxiety disorder (social phobia). Their main advantages are a low risk of dependence and a lesser anticholinergic effect than is seen with TCAs. Their main disadvantage is the higher number of adverse effects, including sexual difficulty, hypotension, and weight gain. A diet low in tyramine must be followed to avoid a hypertensive crisis. Use concomitant medications, including over-the-counter medications, with great caution. Because of the high risk for serotonin syndrome or hypertensive crisis, MAOIs are contraindicated in patients taking selective serotonin reuptake inhibitors; dual serotonin and norepinephrine reuptake inhibitors; tricyclic antidepressants; bupropion (Wellbutrin); mirtazapine (Remeron); buspirone (Buspar); and certain analgesics, vasoconstrictors, sympathomimetics, and anticonvulsants.
Phenelzine is the most commonly used MAOI for anxiety disorders. (Tranylcypromine 30-60 mg/day is also effective.) Phenelzine is usually reserved for patients who cannot tolerate or do not respond to TCAs or SSRIs.
Selegiline is a selective MAO-B inhibitor at lower therapeutic doses. As such, at the target dose of 6 mg per 24 hours, special dietary restrictions are not needed. In addition, the selegiline transdermal patch has the advantage of avoiding the first pass effect, which decreases the impact of CYP high/low-metabolizer status in terms of medication effects and tolerability.
Selected anticonvulsants have been shown to be effective for social anxiety disorder in mostly open-label, uncontrolled clinical trials and may also be useful in the treatment of other phobic disorders.
Gabapentin is a membrane stabilizer and a structural analogue of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA), which, paradoxically, is thought not to exert effects on GABA receptors. It appears to exert action via the alpha-2-delta1 and alpha-2-delta2 auxiliary subunits of voltage-gated calcium channels and has apparent anxiolytic properties.
Pregabalin is a structural derivative of GABA. Its mechanism of action is unknown. It binds with high affinity to alpha-2-delta calcium channel subunits. In vitro, it reduces the calcium-dependent release of several neurotransmitters, possibly by modulating calcium channel function.
The mechanism of action of valproic acid is not established; its activity may be related to increased brain levels of GABA or enhanced GABA action. Valproic acid may also potentiate postsynaptic GABA responses, affect the potassium channel, or exert a direct membrane-stabilizing effect.
American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR). Washington, DC: American Psychiatric Association Press; 2000.
Mathew SJ, Coplan JD, Gorman JM. Neurobiological mechanisms of social anxiety disorder. Am J Psychiatry. 2001 Oct. 158(10):1558-67. [Medline].
Kendler KS, Karkowski LM, Prescott CA. Fears and phobias: reliability and heritability. Psychol Med. 1999 May. 29(3):539-53. [Medline].
Fyer AJ, Mannuzza S, Chapman TF, Liebowitz MR, Klein DF. A direct interview family study of social phobia. Arch Gen Psychiatry. 1993 Apr. 50(4):286-93. [Medline].
Van Houtem CM, Laine ML, Boomsma DI, Ligthart L, van Wijk AJ, De Jongh A. A review and meta-analysis of the heritability of specific phobia subtypes and corresponding fears. J Anxiety Disord. 2013 May. 27(4):379-88. [Medline].
LeBeau RT, Glenn D, Liao B, et al. Specific phobia: a review of DSM-IV specific phobia and preliminary recommendations for DSM-V. Depress Anxiety. 2010 Feb. 27(2):148-67. [Medline].
Linares IM, Trzesniak C, Chagas MH, Hallak JE, Nardi AE, Crippa JA. Neuroimaging in specific phobia disorder: a systematic review of the literature. Rev Bras Psiquiatr. 2012 Mar. 34(1):101-11. [Medline].
Tillfors M, Furmark T, Marteinsdottir I, Fredrikson M. Cerebral blood flow during anticipation of public speaking in social phobia: a PET study. Biol Psychiatry. 2002 Dec 1. 52(11):1113-9. [Medline].
Tillfors M, Furmark T, Marteinsdottir I, Fischer H, Pissiota A, Långström B, et al. Cerebral blood flow in subjects with social phobia during stressful speaking tasks: a PET study. Am J Psychiatry. 2001 Aug. 158(8):1220-6. [Medline].
Lanzenberger RR, Mitterhauser M, Spindelegger C, Wadsak W, Klein N, Mien LK, et al. Reduced serotonin-1A receptor binding in social anxiety disorder. Biol Psychiatry. 2007 May 1. 61(9):1081-9. [Medline].
Lanzenberger R, Wadsak W, Spindelegger C, Mitterhauser M, Akimova E, Mien LK, et al. Cortisol plasma levels in social anxiety disorder patients correlate with serotonin-1A receptor binding in limbic brain regions. Int J Neuropsychopharmacol. 2010 Oct. 13(9):1129-43. [Medline].
Freitas-Ferrari MC, Hallak JE, Trzesniak C, Filho AS, Machado-de-Sousa JP, Chagas MH, et al. Neuroimaging in social anxiety disorder: a systematic review of the literature. Prog Neuropsychopharmacol Biol Psychiatry. 2010 May 30. 34(4):565-80. [Medline].
Ahs F, Pissiota A, Michelgård A, Frans O, Furmark T, Appel L, et al. Disentangling the web of fear: amygdala reactivity and functional connectivity in spider and snake phobia. Psychiatry Res. 2009 May 15. 172(2):103-8. [Medline].
Caseras X, Giampietro V, Lamas A, Brammer M, Vilarroya O, Carmona S, et al. The functional neuroanatomy of blood-injection-injury phobia: a comparison with spider phobics and healthy controls. Psychol Med. 2010 Jan. 40(1):125-34. [Medline].
Straube T, Mentzel HJ, Miltner WH. Waiting for spiders: brain activation during anticipatory anxiety in spider phobics. Neuroimage. 2007 Oct 1. 37(4):1427-36. [Medline].
Kessler RC, Petukhova M, Sampson NA, Zaslavsky AM, Wittchen HU. Twelve-month and lifetime prevalence and lifetime morbid risk of anxiety and mood disorders in the United States. Int J Methods Psychiatr Res. 2012 Sep. 21(3):169-84. [Medline]. [Full Text].
Lewis-Fernández R, Hinton DE, Laria AJ, et al. Culture and the anxiety disorders: recommendations for DSM-V. Depress Anxiety. 2010 Feb. 27(2):212-29. [Medline].
Kessler RC, Berglund P, Demler O, Jin R, Merikangas KR, Walters EE. Lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the National Comorbidity Survey Replication. Arch Gen Psychiatry. 2005 Jun. 62(6):593-602. [Medline].
Wolitzky-Taylor KB, Castriotta N, Lenze EJ, Stanley MA, Craske MG. Anxiety disorders in older adults: a comprehensive review. Depress Anxiety. 2010 Feb. 27(2):190-211. [Medline].
Ruscio AM, Brown TA, Chiu WT, Sareen J, Stein MB, Kessler RC. Social fears and social phobia in the USA: results from the National Comorbidity Survey Replication. Psychol Med. 2008 Jan. 38(1):15-28. [Medline]. [Full Text].
Ollendick TH, King NJ, Muris P. Fears and phobias in children: phenomenology, epidemiology and aetiology. Child Adolesc Ment Health. 2002. 7:98–106.
Wittchen HU, Jacobi F, Rehm J, et al. The size and burden of mental disorders and other disorders of the brain in Europe 2010. Eur Neuropsychopharmacol. 2011 Sep. 21(9):655-79. [Medline].
Beesdo K, Knappe S, Pine DS. Anxiety and anxiety disorders in children and adolescents: developmental issues and implications for DSM-V. Psychiatr Clin North Am. 2009 Sep. 32(3):483-524. [Medline]. [Full Text].
Kessler RC, Chiu WT, Jin R, Ruscio AM, Shear K, Walters EE. The epidemiology of panic attacks, panic disorder, and agoraphobia in the National Comorbidity Survey Replication. Arch Gen Psychiatry. 2006 Apr. 63(4):415-24. [Medline]. [Full Text].
Fehm L, Pelissolo A, Furmark T, Wittchen HU. Size and burden of social phobia in Europe. Eur Neuropsychopharmacol. 2005 Aug. 15(4):453-62. [Medline].
Wittchen HU, Stein MB, Kessler RC. Social fears and social phobia in a community sample of adolescents and young adults: prevalence, risk factors and co-morbidity. Psychol Med. 1999 Mar. 29(2):309-23. [Medline].
Wittchen HU, Gloster AT, Beesdo-Baum K, Fava GA, Craske MG. Agoraphobia: a review of the diagnostic classificatory position and criteria. Depress Anxiety. 2010 Feb. 27(2):113-33. [Medline].
Bruce SE, Yonkers KA, Otto MW, Eisen JL, Weisberg RB, Pagano M, et al. Influence of psychiatric comorbidity on recovery and recurrence in generalized anxiety disorder, social phobia, and panic disorder: a 12-year prospective study. Am J Psychiatry. 2005 Jun. 162(6):1179-87. [Medline].
Schneier FR, Heckelman LR, Garfinkel R, Campeas R, Fallon BA, Gitow A, et al. Functional impairment in social phobia. J Clin Psychiatry. 1994 Aug. 55(8):322-31. [Medline].
Lochner C, Mogotsi M, du Toit PL, Kaminer D, Niehaus DJ, Stein DJ. Quality of life in anxiety disorders: a comparison of obsessive-compulsive disorder, social anxiety disorder, and panic disorder. Psychopathology. 2003 Sep-Oct. 36(5):255-62. [Medline].
Matza LS, Revicki DA, Davidson JR, Stewart JW. Depression with atypical features in the National Comorbidity Survey: classification, description, and consequences. Arch Gen Psychiatry. 2003 Aug. 60(8):817-26. [Medline].
Sareen J, Cox BJ, Afifi TO, de Graaf R, Asmundson GJ, ten Have M, et al. Anxiety disorders and risk for suicidal ideation and suicide attempts: a population-based longitudinal study of adults. Arch Gen Psychiatry. 2005 Nov. 62(11):1249-57. [Medline].
Stein MB, Stein DJ. Social anxiety disorder. Lancet. 2008 Mar 29. 371(9618):1115-25. [Medline].
Beesdo K, Bittner A, Pine DS, Stein MB, Höfler M, Lieb R, et al. Incidence of social anxiety disorder and the consistent risk for secondary depression in the first three decades of life. Arch Gen Psychiatry. 2007 Aug. 64(8):903-12. [Medline].
Magee WJ, Eaton WW, Wittchen HU, McGonagle KA, Kessler RC. Agoraphobia, simple phobia, and social phobia in the National Comorbidity Survey. Arch Gen Psychiatry. 1996 Feb. 53(2):159-68. [Medline].
Liotti G. Phobias of Attachment-Related Inner States in the Psychotherapy of Adult Survivors of Childhood Complex Trauma. J Clin Psychol. 2013 Aug 28. [Medline].
Baldwin DS, Anderson IM, Nutt DJ, Bandelow B, Bond A, Davidson JR, et al. Evidence-based guidelines for the pharmacological treatment of anxiety disorders: recommendations from the British Association for Psychopharmacology. J Psychopharmacol. 2005 Nov. 19(6):567-96. [Medline].
de Beurs E, van Balkom AJ, Van Dyck R, Lange A. Long-term outcome of pharmacological and psychological treatment for panic disorder with agoraphobia: a 2-year naturalistic follow-up. Acta Psychiatr Scand. 1999 Jan. 99(1):59-67. [Medline].
Pelissolo A. [Efficacy and tolerability of escitalopram in anxiety disorders: a review]. Encephale. 2008 Sep. 34(4):400-8. [Medline].
National Prescribing Service Limited. Escitalopram (Lexapro, Esipram) for generalised anxiety disorder and social anxiety disorder (social phobia). NPS RADAR. Available at http://bit.ly/dOARMJ.
Stein DJ, Ipser JC, van Balkom AJ. Pharmacotherapy for social anxiety disorder. Cochrane Review. Chichester, UK: John Wiley and Sons, Ltd; 2009.
Westenberg HG. Recent advances in understanding and treating social anxiety disorder. CNS Spectr. 2009 Feb. 14(2 Suppl 3):24-33. [Medline].
Ravindran LN, Stein MB. The pharmacologic treatment of anxiety disorders: a review of progress. J Clin Psychiatry. 2010 Jul. 71(7):839-54. [Medline].
Davidson JR. Pharmacotherapy of social anxiety disorder: what does the evidence tell us?. J Clin Psychiatry. 2006. 67 Suppl 12:20-6. [Medline].
Offidani E, Guidi J, Tomba E, Fava GA. Efficacy and Tolerability of Benzodiazepines versus Antidepressants in Anxiety Disorders: A Systematic Review and Meta-Analysis. Psychother Psychosom. 2013 Sep 20. 82(6):355-362. [Medline].
Van Ameringen M, Allgulander C, Bandelow B, Greist JH, Hollander E, Montgomery SA, et al. WCA recommendations for the long-term treatment of social phobia. CNS Spectr. 2003 Aug. 8(8 Suppl 1):40-52. [Medline].
Practice guideline for the treatment of patients with panic disorder. Work Group on Panic Disorder. American Psychiatric Association. Am J Psychiatry. 1998 May. 155(5 Suppl):1-34. [Medline].
Pohl RB, Wolkow RM, Clary CM. Sertraline in the treatment of panic disorder: a double-blind multicenter trial. Am J Psychiatry. 1998 Sep. 155(9):1189-95. [Medline].
Michelson D, Lydiard RB, Pollack MH, Tamura RN, Hoog SL, Tepner R, et al. Outcome assessment and clinical improvement in panic disorder: evidence from a randomized controlled trial of fluoxetine and placebo. The Fluoxetine Panic Disorder Study Group. Am J Psychiatry. 1998 Nov. 155(11):1570-7. [Medline].
Uhlenhuth EH, Balter MB, Ban TA, Yang K. International study of expert judgment on therapeutic use of benzodiazepines and other psychotherapeutic medications: VI. Trends in recommendations for the pharmacotherapy of anxiety disorders, 1992-1997. Depress Anxiety. 1999. 9(3):107-16. [Medline].
Shear MK, Beidel DC. Psychotherapy in the overall management strategy for social anxiety disorder. J Clin Psychiatry. 1998. 59 Suppl 17:39-46. [Medline].
Barlow JH, Ellard DR, Hainsworth JM, Jones FR, Fisher A. A review of self-management interventions for panic disorders, phobias and obsessive-compulsive disorders. Acta Psychiatr Scand. 2005 Apr. 111(4):272-85. [Medline].
Masia Warner C, Fisher PH, Shrout PE, Rathor S, Klein RG. Treating adolescents with social anxiety disorder in school: an attention control trial. J Child Psychol Psychiatry. 2007 Jul. 48(7):676-86. [Medline].
Bunnell BE, Beidel DC, Mesa F. A Randomized Trial of Attention Training for Generalized Social Phobia: Does Attention Training Change Social Behavior?. Behav Ther. 2013 Dec. 44(4):662-673. [Medline].
Ayala ES, Meuret AE, Ritz T. Treatments for blood-injury-injection phobia: a critical review of current evidence. J Psychiatr Res. 2009 Oct. 43(15):1235-42. [Medline].
Rothbaum BO, Anderson P, Zimand E, Hodges L, Lang D, Wilson J. Virtual reality exposure therapy and standard (in vivo) exposure therapy in the treatment of fear of flying. Behav Ther. 2006 Mar. 37(1):80-90. [Medline].
Paquette V, Lévesque J, Mensour B, Leroux JM, Beaudoin G, Bourgouin P, et al. "Change the mind and you change the brain": effects of cognitive-behavioral therapy on the neural correlates of spider phobia. Neuroimage. 2003 Feb. 18(2):401-9. [Medline].
Schienle A, Schäfer A, Hermann A, Rohrmann S, Vaitl D. Symptom provocation and reduction in patients suffering from spider phobia: an fMRI study on exposure therapy. Eur Arch Psychiatry Clin Neurosci. 2007 Dec. 257(8):486-93. [Medline].
Sánchez-Meca J, Rosa-Alcázar AI, Marín-Martínez F, Gómez-Conesa A. Psychological treatment of panic disorder with or without agoraphobia: a meta-analysis. Clin Psychol Rev. 2010 Feb. 30(1):37-50. [Medline].
Hudson C, Hudson S, MacKenzie J. Protein-source tryptophan as an efficacious treatment for social anxiety disorder: a pilot study. Can J Physiol Pharmacol. 2007 Sep. 85(9):928-32. [Medline].