Emerging drugs for panic disorder

Expert Opinion on Emerging Drugs

Volumn 16, Issue 4, 2011, Pages 631-645

  Perna, Giampaolo ^a,b,c   Guerriero, Giuseppe ^a   Caldirola, Daniela ^a  

^a San Benedetto Hospital   (Italy)

^b MAASTRICHT UNIVERSITY   (Netherlands)

^c UNIVERSITY OF MIAMI MILLER SCHOOL OF MEDICINE   (United States)

Author keywords

Anticonvulsants; Atypical antipsychotics; Cholinergic system; D cycloserine; Drug development; Glutamate receptor; Orexin; Panic disorder; Treatment

Indexed keywords

ANTICONVULSIVE AGENT; BENZODIAZEPINE; CITALOPRAM; CYCLOSERINE; DULOXETINE; EGLUMETAD; EMAPUNIL; ETIRACETAM; FLUOXETINE; FLUVOXAMINE; METABOTROPIC RECEPTOR AGONIST; MILNACIPRAN; MIRTAZAPINE; NEUROKININ 1 RECEPTOR ANTAGONIST; NEUROKININ 2 RECEPTOR ANTAGONIST; OREXIN; PAROXETINE; PINDOLOL; REBOXETINE; RISPERIDONE; SEROTONIN UPTAKE INHIBITOR; SERTRALINE; TRICYCLIC ANTIDEPRESSANT AGENT; VENLAFAXINE;

AMYGDALOID NUCLEUS; ANXIETY DISORDER; DRUG EFFICACY; EMOTION; ENDOPHENOTYPE; GENETIC HETEROGENEITY; HUMAN; HYPOTHALAMUS; MORBIDITY; NERVE CELL; NONHUMAN; PANIC; PATHOPHYSIOLOGY; PHASE 2 CLINICAL TRIAL (TOPIC); REVIEW;

CLINICAL TRIALS AS TOPIC; DRUG DESIGN; DRUGS, INVESTIGATIONAL; HUMANS; PANIC DISORDER; PSYCHOTROPIC DRUGS; RECEPTORS, METABOTROPIC GLUTAMATE; TREATMENT OUTCOME;

EID: 84555191754     PISSN: 14728214     EISSN: None     Source Type: Journal    
DOI: 10.1517/14728214.2011.628313     Document Type: Review

References (129)

1. Westenberg HGM, Liebowitz MR. Overview of panic and social anxiety disorders. J Clin Psychiatry 2004;65(SUPPL. 14):22-6
2. Perna G. Understanding anxiety disorders: from psychology to psychopathology of defence mechanisms from threat. Riv Psichiatr; In press
3. Roberson-Nay R, Kendler KS. Panic disorder and its subtypes: a comprehensive analysis of panic symptom heterogeneity using epidemiological and treatment seeking samples. Psychol Med 2011;published online 18 April 2011; doi:10.1017/S0033291711000547.
4. Klein DF. False suffocation alarms, spontaneous panics, and related conditions. An integrative hypothesis. Arch Gen Psychiatry 1993;50:306-17 (Pubitemid 23115374)
5. Esquivel G, Schruers KR, Maddock RJ, et al. Acids in the brain: a factor in panic? J Psychopharmacol (Oxford) 2010;24:639-47
6. Perna G, Caldirola D, Bellodi L. Panic disorder: from respiration to the homeostatic brain. Acta Neuropsychiatr 2004;16:57-67 (Pubitemid 38405260)
7. Gorman JM, Kent JM, Sullivan GM, Coplan JD. Neuroanatomical hypothesis of panic disorder, revised. Am J Psychiatry 2000;157:493-505 (Pubitemid 30191187)
8. Freire RC, Hallak JE, Crippa JA, Nardi AE. New treatment options for panic disorder: clinical trials from 2000 to 2010. Expert Opin Pharmacother 2011;12:1419-28
9. Battaglia M, Ogliari A. Anxiety and panic: from human studies to animal research and back. Neurosci Biobehav Rev 2005;29:169-79 (Pubitemid 40094586)
10. American Psychiatric Association. Practice guideline for the treatment of patients with panic disorder. 2nd edition. American Psychiatric Publishing, Inc.; Washington, DC: 2009
11. Van Apeldoorn FJ, van Hout WJPJ, Mersch PPA, et al. Is a combined therapy more effective than either CBT or SSRI alone? Results of a multicenter trial on panic disorder with or without agoraphobia. Acta Psychiatr Scand 2008;117:260-70 (Pubitemid 351347467)
12. Yates WR. Phenomenology and epidemiology of panic disorder. Ann Clin Psychiatry 2009;21:95-102
13. Generalised anxiety disorder and panic disorder (with or without agoraphobia) in adults: management in primary, secondary and community care. (Clinicalguideline113) National Institute for Health and Clinical Excellence. London: 2011. Available from: http://guidance.nice.org.uk/CG113 Last accessed 21 May 2011
14. McHugh RK, Smits JAJ, Otto MW. Empirically supported treatments for panic disorder. Psychiatr Clin North Am 2009;32:593-610
15. Bouton ME, Mineka S, Barlow DH. A modern learning theory perspective on the etiology of panic disorder. Psychol Rev 2001;108:4-32 (Pubitemid 33604124)
16. Richerson GB. Serotonergic neurons as carbon dioxide sensors that maintain pH homeostasis. Nat Rev Neurosci 2004;5:449-61 (Pubitemid 38715512)
17. Bertani A, Perna G, Arancio C, et al. Pharmacologic effect of imipramine, paroxetine, and sertraline on 35% carbon dioxide hypersensitivity in panic patients: a double-blind, random, placebo-controlled study. J Clin Psychopharmacol 1997;17:97-101 (Pubitemid 27148304)
18. Schruers K, van Diest R, Overbeek T, Griez E. Acute L-5-hydroxytryptophan administration inhibits carbon dioxide-induced panic in panic disorder patients. Psychiatry Res 2002;113:237-43 (Pubitemid 36136046)
19. Schruers K, Klaassen T, Pols H, et al. Effects of tryptophan depletion on carbon dioxide provoked panic in panic disorder patients. Psychiatry Res 2000;93:179-87 (Pubitemid 30175948)
20. Bailey JE. Does the brain noradrenaline network mediate the effects of the CO2 challenge? J Psychopharmacol 2003;17:252-9 (Pubitemid 37150829)
21. Rentero N, Bruandet N, Pequignot JM, Quintin L. Catechol changes in the rat rostral ventrolateral medulla following changes in systemic CO2. Am J Physiol 1997;273:R947-55
22. Perna G, Bertani A, Caldirola D, et al. Modulation of hyperreactivity to 35% CO2 after one week of treatment with paroxetine and reboxetine: a double-blind, randomized study. J Clin Psychopharmacol 2004;24:277-82 (Pubitemid 38658035)
23. Bailey JE, Papadopoulos A, Seddon K, Nutt DJ. A comparison of the effects of a subtype selective and non-selective benzodiazepine receptor agonist in two CO(2) models of experimental human anxiety. J Psychopharmacol 2009;23:117-22
24. Shekhar A, Keim SR, Simon JR, McBride WJ. Dorsomedial hypothalamic GABA dysfunction produces physiological arousal following sodium lactate infusions. Pharmacol Biochem Behav 1996;55:249-56 (Pubitemid 26414107)
25. Nardi AE, Valenca AM, Nascimento I, et al. Double-blind acute clonazepam vs. placebo in carbon dioxide-induced panic attacks. Psychiatry Res 2000;94:179-84 (Pubitemid 30243105)
26. Hasler G, Nugent AC, Carlson PJ, et al. Altered cerebral gamma-aminobutyric acid type A-benzodiazepine receptor binding in panic disorder determined by 11Cflumazenil positron emission tomography. Arch Gen Psychiatry 2008;65:1166-75
27. Perna G, Bertani A, Caldirola D, et al. Antipanic drug modulation of 35% CO2 hyperreactivity and short-term treatment outcome. J Clin Psychopharmacol 2002;22:300-8 (Pubitemid 34546846)
28. Bertani A, Caldirola D, Bussi R, et al. The 35% CO2 hyperreactivity and clinical symptomatology in patients with panic disorder after 1 week of treatment with citalopram: an open study. J Clin Psychopharmacol 2001;21:262-7 (Pubitemid 32452930)
29. Perna G, Bertani A, Caldirola D, et al. A comparison of citalopram and paroxetine in the treatment of panic disorder: a randomized, single-blind study. Pharmacopsychiatry 2001;34:85-90 (Pubitemid 32531127)
30. Pollack M, Mangano R, Entsuah R, et al. A randomized controlled trial of venlafaxine ER and paroxetine in the treatment of outpatients with panic disorder. Psychopharmacology (Berl) 2007;194:233-42 (Pubitemid 47457944)
31. Liebowitz MR, Asnis G, Mangano R, Tzanis E. A double-blind, placebo-controlled, parallel-group, flexible-dose study of venlafaxine extended release capsules in adult outpatients with panic disorder. J Clin Psychiatry 2009;70:550-61
32. Bertani A, Bellodi L, Bussi R, et al. The effect of one-week treatment with venlafaxine on 35% CO2 hyperreactivity in patients with panic disorder: an open study. J Clin Psychopharmacol 2003;23:106-8 (Pubitemid 36164436)
33. Bakker A, van Balkom AJLM, Spinhoven P. SSRIs vs. TCAs in the treatment of panic disorder: a meta-analysis. Acta Psychiatr Scand 2002;106:163-7
34. Perna G, Bertani A, Gabriele A, et al. Modification of 35% carbon dioxide hypersensitivity across one week of treatment with clomipramine and fluvoxamine: a double-blind, randomized, placebo-controlled study. J Clin Psychopharmacol 1997;17:173-8 (Pubitemid 27261771)
35. Sasson Y, Iancu I, Fux M, et al. A double-blind crossover comparison of clomipramine and desipramine in the treatment of panic disorder. Eur Neuropsychopharmacol 1999;9:191-6 (Pubitemid 29114923)
36. Nardi AE, Perna G. Clonazepam in the treatment of psychiatric disorders: an update. Int Clin Psychopharmacol 2006;21:131-42 (Pubitemid 43740304)
37. Nardi AE, Valenca AM, Freire RC, et al. Psychopharmacotherapy of panic disorder: 8-week randomized trial with clonazepam and paroxetine. Braz J Med Biol Res 2011;44:366-73
38. Nardi AE, Valenca AM, Nascimento I, et al. A three-year follow-up study of patients with the respiratory subtype of panic disorder after treatment with clonazepam. Psychiatry Res 2005;137:61-70 (Pubitemid 41550129)
39. Goddard AW, Brouette T, Almai A, et al. Early coadministration of clonazepam with sertraline for panic disorder. Arch Gen Psychiatry 2001;58:681-6 (Pubitemid 32651693)
40. Pollack MH, Simon NM, Worthington JJ, et al. Combined paroxetine and clonazepam treatment strategies compared to paroxetine monotherapy for panic disorder. J Psychopharmacol 2003;17:276-82 (Pubitemid 37150836)
41. Otto MW, Bruce SE, Deckersbach T. Benzodiazepine use, cognitive impairment, and cognitive-behavioral therapy for anxiety disorders: issues in the treatment of a patient in need. J Clin Psychiatry 2005;66(SUPPL. 2):34-8 (Pubitemid 40343679)
42. Serretti A, Chiesa A, Calati R, et al. Novel antidepressants and panic disorder: evidence beyond current guidelines. Neuropsychobiology 2011;63:1-7
43. Trivedi MH, Desaiah D, Ossanna MJ, et al. Clinical evidence for serotonin and norepinephrine reuptake inhibition of duloxetine. Int Clin Psychopharmacol 2008;23:161-9 (Pubitemid 351535907)
44. Mancini M, Perna G, Rossi A, Petralia A. Use of duloxetine in patients with an anxiety disorder, or with comorbid anxiety and major depressive disorder: a review of the literature. Expert Opin Pharmacother 2010;11:1167-81
45. Cia AH, Brizuela JA, Cascardo E, Varela MF. Clonazepam and milnacipran in the treatment of patients with panic disorder and comorbid major depression. Prim Care Community Psychiatry 2006;11:51-6 (Pubitemid 44803631)
46. Blaya C, Seganfredo AC, Dornelles M, et al. The efficacy of milnacipran in panic disorder: an open trial. Int Clin Psychopharmacol 2007;22:153-8 (Pubitemid 46559871)
47. De Boer T. The pharmacologic profile of mirtazapine. J Clin Psychiatry 1996;57:19-25 (Pubitemid 26177340)
48. Carpenter LL, Leon Z, Yasmin S, Price LH. Clinical experience with mirtazapine in the treatment of panic disorder. Ann Clin Psychiatry 1999;11:81-6 (Pubitemid 29343106)
49. Sarchiapone M, Amore M, De Risio S, et al. Mirtazapine in the treatment of panic disorder: an open-label trial. Int Clin Psychopharmacol 2003;18:35-8 (Pubitemid 36127059)
50. Montanes-Rada F, De Lucas-Taracena MT, Sanchez-Romero S. Mirtazapine versus paroxetine in panic disorder: an open study. Int J Psychol Clin Pract 2005;9:87-93 (Pubitemid 40874102)
51. Brunello N, Racagni G. Rationale for the development of noradrenaline reuptake inhibitors. Hum Psychopharmacol Clin Exp 1998;13:S13-19 (Pubitemid 28109322)
52. Dannon P, Iancu I, Grunhaus L. The efficacy of reboxetine in the treatment-refractory patients with panic disorder: an open label study. Hum Psychopharmacol 2002;17:329-33 (Pubitemid 35189814)
53. Seedat S, van Rheede van Oudtshoorn E, Muller JE, et al. Reboxetine and citalopram in panic disorder: a single-blind, cross-over, flexible-dose pilot study. Int Clin Psychopharmacol 2003;18:279-84 (Pubitemid 37041412)
54. Bertani A, Perna G, Migliarese G, et al. Comparison of the treatment with paroxetine and reboxetine in panic disorder: a randomized, single-blind study. Pharmacopsychiatry 2004;37:206-10 (Pubitemid 39286922)
55. Javitt DC. Glutamate as a therapeutic target in psychiatric disorders. Mol Psychiatry 2004;9:984-97 (Pubitemid 39524288)
56. Schoepp DD, Wright RA, Levine LR, et al. LY354740, an mGlu2/3 receptor agonist as a novel approach to Treat Anxiety/Stress. Stress 2003;6:189-97 (Pubitemid 37210425)
57. Shekhar A, Keim SR. LY354740, a potent group II metabotropic glutamate receptor agonist prevents lactate-induced panic-like response in panic-prone rats. Neuropharmacology 2000;39:1139-46 (Pubitemid 30173179)
58. Otto MW, Tolin DF, Simon NM, et al. Efficacy of d-Cycloserine for enhancing response to Cognitive-behavior therapy for panic disorder. Biol Psychiatry 2010;67:365-70
59. National Institute of Mental Health (NIMH). Exposure, D-Cycloserine Enhancement, and Genetic Modulators in (DCSPanic). In: ClinicalTrials.gov Internet. Bethesda (MD): National Library of Medicine (US) 2008. NLM Identifier: NCT00790868 Available from: http://clinicaltrials.gov/ct2/show/NCT00790868 Cited 22 May 2011
60. Stahl's Essential Psychopharmacology: Neuroscientific Basis & Practical Applications. 3rd edition. CUP; Cambridge: 2008
61. Blier P, Szabo ST. Potential mechanisms of action of atypical antipsychotic medications in treatment-resistant depression and anxiety. J Clin Psychiatry 2005;66:30-40 (Pubitemid 43004173)
62. Inoue T, Tsuchiya K, Koyama T. Effects of typical and atypical antipsychotic drugs on freezing behavior induced by conditioned fear. Pharmacol Biochem Behav 1996;55:195-201 (Pubitemid 26414100)
63. Mula M, Pini S, Cassano GB. The role of anticonvulsant drugs in anxiety disorders. J Clin Psychopharmacol 2007;27:263-72
64. Lindner Center of HOPE, UCB, Inc., University of Cincinnati.Levetiracetam Treatment of and Lactate-Induced Panic Attacks. In: ClinicalTrials.gov Internet. Bethesda (MD): National Library of Medicine (US) 2006. NLM Identifier: NCT00279617. Available from: http://clinicaltrials.gov/ct2/show/NCT00279617 Cited 22 May 2011
65. Grillon C, Cordova J, Levine LR, Morgan CA. Anxiolytic effects of a novel group II metabotropic glutamate receptor agonist (LY354740) in the fear-potentiated startle paradigm in humans. Psychopharmacology (Berl) 2003;168:446-54 (Pubitemid 36994028)
66. Levine L, Gaydos B, Sheehan D, Goddard A. The mGlu2/3 receptor agonist, LY354740, reduces panic anxiety induced by a CO2 challenge in patients diagnosed with panic disorder. Neuropharmacology 2002;43:294
67. Bergink V, Westenberg HGM. Metabotropic glutamate II receptor agonists in panic disorder: a double blind clinical trial with LY354740. Int Clin Psychopharmacol 2002;43:294-3
68. Perkins EJ, Abraham T. Pharmacokinetics, Metabolism, and Excretion of the PepT1-Targeted Prodrug (1S, 2S, 5R, 6S)-2-(2¢S)-(2-Amino) propionyl aminobicyclo 3.1. 0. hexen-2,6-dicarboxylic acid (LY544344) in Rats and Dogs: Assessment of First-pass Bioactivation and Dose-Linearity. Drug Metab Dispos 2007;published online 23 July 2007; doi:10.1124/dmd.107.016154 (Pubitemid 47481585)
69. Rorick-Kehn LM, Perkins EJ, Knitowski KM, et al. Improved bioavailability of the mGlu2/3 receptor agonist LY354740 using a prodrug strategy: in vivo pharmacology of LY544344. J Pharmacol Exp Ther 2006;316:905-13 (Pubitemid 43131021)
70. Davis M, Gendelman DS, Tischler MD, Gendelman PM. A primary acoustic startle circuit: lesion and stimulation studies. J Neurosci 1982;2:791-805 (Pubitemid 12064613)
71. Ressler KJ, Rothbaum BO, Tannenbaum L, et al. Cognitive enhancers as adjuncts to psychotherapy: use of D-cycloserine in phobic individuals to facilitate extinction of fear. Arch Gen Psychiatry 2004;61:1136-44 (Pubitemid 39463415)
72. Siegmund A, Golfels F, Finck C, et al. D-Cycloserine does not improve but might slightly speed up the outcome of in-vivo exposure therapy in patients with severe agoraphobia and panic disorder in a randomized double blind clinical trial. J Psychiatr Res 2011;published online 5 March 2011; doi:10.1016/j. jpsychires.2011.01.020.
73. Lamberty Y, Falter U, Gower AJ, Klitgaard H. Anxiolytic profile of the antiepileptic drug levetiracetam in the Vogel conflict test in the rat. Eur J Pharmacol 2003;469:97-102 (Pubitemid 36629555)
74. Lamberty Y, Gower AJ, Klitgaard H. The new antiepileptic drug levetiracetam normalises chlordiazepoxide withdrawal-induced anxiety in mice. Eur J Pharmacol 2002;439:101-6 (Pubitemid 34286612)
75. Papp LA. Safety and efficacy of levetiracetam for patients with panic disorder: results of an open-label, fixed-flexible dose study. J Clin Psychiatry 2006;67:1573-6 (Pubitemid 44787440)
76. Gorenstein EE, Kleber MS, Mohlman J, et al. Cognitive-behavioral therapy for management of anxiety and medication taper in older adults. Am J Geriatr Psychiatry 2005;13:901-9 (Pubitemid 46638679)
77. Brawman-Mintzer O, Knapp RG, Nietert PJ. Adjunctive risperidone in generalized anxiety disorder: a double-blind, placebo-controlled study. J Clin Psychiatry 2005;66:1321-5 (Pubitemid 41546513)
78. Erzegovesi S, Guglielmo E, Siliprandi F, Bellodi L. Low-dose risperidone augmentation of fluvoxamine treatment in obsessive-compulsive disorder: a double-blind, placebo-controlled study. Eur Neuropsychopharmacol 2005;15:69-74 (Pubitemid 39574401)
79. Prosser JM, Yard S, Steele A, et al. A comparison of low-dose risperidone to paroxetine in the treatment of panic attacks: a randomized, single-blind study. BMC Psychiatry 2009;9:25
80. Sepede G, De Berardis D, Gambi F, et al. Olanzapine augmentation in treatment-resistant panic disorder: a 12-week, fixed-dose, open-label trial. J Clin Psychopharmacol 2006;26:45-9 (Pubitemid 43167090)
81. Hollifield M, Thompson PM, Ruiz JE, Uhlenhuth EH. Potential effectiveness and safety of olanzapine in refractory panic disorder. Depress Anxiety 2005;21:33-40 (Pubitemid 40614547)
82. Indiana University, AstraZeneca. A Study of Quetiapine SR (Seroquel SR) to Treat SSRI-Resistant, Comorbid Panic Disorder Patients. In: ClinicalTrials.gov Internet. Bethesda (MD): National Library of Medicine (US) 2008. NLM Identifier: NCT00619892. Available from: http://clinicaltrials.gov/ ct2/show/NCT00619892 Cited 22 May 2011
83. VA Palo Alto Health Care System, Pfizer, University of South Florida, Lindner Center of HOPE.Ziprasidone in Bipolar Disorder With Comorbid Lifetime Panic or Generalized Anxiety Disorder(GAD) (Pfizer Anxiety). In: ClinicalTrials.gov Internet. Bethesda (MD): National Library of Medicine (US) 2008. NLM Identifier: NCT01172652. Available from: http://clinicaltrials.gov/ ct2/show/NCT01172652 Cited 22 May 2011
84. Johnson PL, Truitt W, Fitz SD, et al. A key role for orexin in panic anxiety. Nat Med 2010;16:111-U149
85. Salomon RM, Ripley B, Kennedy JS, et al. Diurnal variation of cerebrospinal fluid hypocretin-1 (Orexin-A) levels in control and depressed subjects. Biol Psychiatry 2003;54:96-104 (Pubitemid 36859768)
86. Nattie E. CO2, brainstem chemoreceptors and breathing. Prog Neurobiol 1999;59:299-331
87. Battaglia M, Bertella S, Ogliari A, et al. Modulation by muscarinic antagonists of the response to carbon dioxide challenge in panic disorder. Arch Gen Psychiatry 2001;58:114-19 (Pubitemid 32142748)
88. Kaufer D, Friedman A, Seidman S, Soreq H. Acute stress facilitates long-lasting changes in cholinergic gene expression. Nature 1998;393:373-7 (Pubitemid 28269711)
89. Meshorer E, Erb C, Gazit R, et al. Alternative splicing and neuritic mRNA translocation under long-term neuronal hypersensitivity. Science 2002;295:508-12 (Pubitemid 34101643)
90. Preter M, Klein D. Panic, suffocation false alarms, separation anxiety and endogenous opioids. Prog Neuropsychopharmacol Biol Psychiatry 2008;32:603-12 (Pubitemid 351312351)
91. Preter M, Lee SH, Petkova E, et al. Controlled cross-over study in normal subjects of naloxone-preceding-lactate infusions; respiratory and subjective responses: relationship to endogenous opioid system, suffocation false alarm theory and childhood parental loss. Psychol Med 2011;41:385-93
92. Borkowski AH, Barnes DC, Blanchette DR, et al. Interaction between delta opioid receptors and benzodiazepines in CO(2)-induced respiratory responses in mice. Brain Res 2011;published online 28 April 2011; doi: 10.1016/j.brainres. 2011.04.042
93. Risbrough VB, Stein MB. Role of corticotropin releasing factor in anxiety disorders: a translational research perspective. Horm Behav 2006;50:550-61 (Pubitemid 44307112)
94. Choi S, Kim S, Park S, et al. Doxapram increases corticotropin-releasing factor immunoreactivity and mRNA expression in the rat central nucleus of the amygdala. Peptides 2005;26:2246-51 (Pubitemid 41584091)
95. Keck ME, Kern N, Erhardt A, et al. Combined effects of exonic polymorphisms in CRHR1 and AVPR1B genes in a case/control study for panic disorder. Am J Med Genet B Neuropsychiatr Genet 2008;147B:1196-204
96. Shekhar A, Johnson PL, Fitz SD, et al. A selective, non-peptide CRF receptor 1 antagonist prevents sodium lactate-induced acute panic-like responses. Int J Neuropsychopharmacol 2011;14:355-65
97. Rupprecht R, Holsboer F. Neuroactive steroids: mechanisms of action and neuropsychopharmacological perspectives. Trends Neurosci 1999;22:410-16 (Pubitemid 29453646)
98. Belelli D, Lambert JJ. Neurosteroids: endogenous regulators of the GABA(A) receptor. Nat Rev Neurosci 2005;6:565-75 (Pubitemid 40942823)
99. Carboni E, Wieland S, Lan N, Gee K. Anxiolytic properties of endogenously occurring pregnanediols in two rodent models of anxiety. Psychopharmacology (Berl) 1996;126:173-8 (Pubitemid 26246768)
100. Strohle A, Romeo E, di Michele F, et al. Induced panic attacks shift gamma-aminobutyric acid type A receptor modulatory neuroactive steroid composition in patients with panic disorder: preliminary results. Arch Gen Psychiatry 2003;60:161-8 (Pubitemid 36173122)
101. Brambilla F, Mellado C, Alciati A, et al. Plasma concentrations of anxiolytic neuroactive steroids in men with panic disorder. Psychiatry Res 2005;135:185-90 (Pubitemid 40984610)
102. Zwanzger P, Eser D, Romeo E, et al. Changes in CCK-4 induced panic after treatment with the GABA-reuptake inhibitor tiagabine are associated with an increase in 3alpha,5alpha-tetrahydrodeoxycorticosterone concentrations. Psychoneuroendocrinology 2009;34:1586-9
103. Papadopoulos V, Baraldi M, Guilarte TR, et al. Translocator protein (18 kDa): new nomenclature for the peripheral-type benzodiazepine receptor based on its structure and molecular function. Trends Pharmacol Sci 2006;27:402-9 (Pubitemid 44069585)
104. Verleye M, Akwa Y, Liere P, et al. The anxiolytic etifoxine activates the peripheral benzodiazepine receptor and increases the neurosteroid levels in rat brain. Pharmacol Biochem Behav 2005;82:712-20 (Pubitemid 43184049)
105. Kita A, Kohayakawa H, Kinoshita T, et al. Antianxiety and antidepressant-like effects of AC-5216, a novel mitochondrial benzodiazepine receptor ligand. Br J Pharmacol 2004;142:1059-72 (Pubitemid 39093001)
106. Rupprecht R, Rammes G, Eser D, et al. Translocator Protein (18 kD) as target for Anxiolytics without benzodiazepine-like side effects. Science 2009;325:490-3
107. Czeh B, Fuchs E, Simon M. NK1 receptor antagonists under investigation for the treatment of affective disorders. Expert Opin Investig Drugs 2006;15:479-86
108. Ebner K, Sartori SB, Singewald N. Tachykinin receptors as therapeutic targets in Stress-Related disorders. Curr Pharm Des 2009;15:1647-74
109. Kronenberg G, Berger P, Tauber R, et al. Randomized, double-blind study of SR142801 (Osanetant). A novel neurokinin-3 (NK3) receptor antagonist in panic disorder with pre-and posttreatment cholecystokinin tetrapeptide (CCK-4) challenges. Pharmacopsychiatry 2005;38:24-9 (Pubitemid 40278643)
110. Fujimura Y, Yasuno F, Farris A, et al. Decreased neurokinin-1 (substance P) receptor binding in patients with panic disorder: positron emission tomographic study with 18FSPA-RQ. Biol Psychiatry 2009;66(1):94-7
111. Furmark T, Appel L, Michelgard A, et al. Cerebral blood flow changes after treatment of social phobia with the neurokinin-1 antagonist GR205171, citalopram, or placebo. Biol Psychiatry 2005;58:132-42 (Pubitemid 41008130)
112. Keller M, Montgomery S, Ball W, et al. Lack of efficacy of the substance p (neurokinin1 receptor) antagonist aprepitant in the treatment of major depressive disorder. Biol Psychiatry 2006;59:216-23 (Pubitemid 43208967)
113. Charney DS, Heninger GR, Jatlow PI. Increased anxiogenic effects of caffeine in panic disorders. Arch Gen Psychiatry 1985;42:233-43 (Pubitemid 15016112)
114. Hohoff C, Mullings EL, Heatherley SV, et al. Adenosine A(2A) receptor gene: evidence for association of risk variants with panic disorder and anxious personality. J Psychiatr Res 2010;44:930-7
115. Lopes LV, Sebastiao AM, Ribeiro JA. Adenosine and Related Drugs in Brain Diseases: present and future in clinical trials. Curr Top Med Chem 2011;11:1087-101
116. Artigas F, Perez V, Alvarez E. Pindolol induces a rapid improvement of depressed patients treated with serotonin reuptake inhibitors. Arch Gen Psychiatry 1994;51:248-51 (Pubitemid 24081512)
117. Zohar J, Dannon P, Sasson Y, et al. Pindolol augmentation in treatment-resistant panic disorder and obsessive-compulsive disorder. Eur Neuropsychopharmacol 1998;8:S99
118. Hirschmann S, Dannon PN, Iancu I, et al. Pindolol augmentation in patients with treatment-resistant panic disorder: A double-blind, placebo-controlled trial. J Clin Psychopharmacol 2000;20:556-9
119. Van Vliet I, Westenberg H, Boer den J. Pindolol does not augment the panicolytic effects of fluvoxamine in panic disorders patients. Eur Neuropsychopharmacol 1998;8:S257-8
120. Sela VR, Biesdorf C, Ramos DH, et al. Serotonin-1A receptors in the dorsal periaqueductal gray matter mediate the panicolytic-like effect of pindolol and paroxetine combination in the elevated T-maze. Neurosci Lett 2011;495:63-6
121. Freire RC, Perna G, Nardi AE. Panic disorder respiratory subtype: psychopathology, laboratory challenge tests, and response to treatment. Harv Rev Psychiatry 2010;18:220-9
122. Caldirola D, Teggi R, Bondi S, Lopes F. Is there a hypersensitive visual alarm system in panic disorder? Psychiatry Res 2011;187:387-91
123. Yeragani VK, Rao R, Tancer M, Uhde T. Paroxetine decreases respiratory irregularity of linear and nonlinear measures of respiration in patients with panic disorder. A preliminary report. Neuropsychobiology 2004;49:53-7 (Pubitemid 38253128)
124. Perna G, Alpini D, Caldirola D, et al. Serotonergic modulation of the balance system in panic disorder: an open study. Depress Anxiety 2003;17:101-6 (Pubitemid 36407106)
125. Liebowitz MR, Fyer AJ, Gorman JM, et al. Lactate provocation of panic attacks. I. Clinical and behavioral findings. Arch Gen Psychiatry 1984;41:764-70 (Pubitemid 14092254)
126. Gorman JM, Askanazi J, Liebowitz MR, et al. Response to hyperventilation in a group of patients with panic disorder. Am J Psychiatry 1984;141:857-61 (Pubitemid 14078996)
127. D'Amato FR, Zanettini C, Lampis V, et al. Unstable maternal environment, separation anxiety, and heightened CO2 sensitivity induced by gene-by-environment interplay. PLoS ONE 2011;6(4):e18637
128. Johnson PL, Shekhar A. Panic-prone state induced in rats with GABA dysfunction in the dorsomedial hypothalamus is mediated by NMDA receptors. J Neurosci 2006;26:7093-104 (Pubitemid 44309876)
129. Lim LW, Blokland A, Tan S, et al. Attenuation of fear-like response by escitalopram treatment after electrical stimulation of the midbrain dorsolateral periaqueductal gray. Exp Neurol 2010;226:293-300