Future Treatments for Depression, Anxiety, Sleep Disorders, Psychosis, and ADHD

This list was graciously provided by JR Becker ([email protected]). Some additions have been made by Shawn Thomas ([email protected]). Please send additions or corrections to [email protected]

Information about recent approvals can be obtained from the FDA Center for Drug Evaluation and Research. For information about already marketed in the US, see Neurotransmitter.net's Drug Reference for FDA Approved Psychiatric Drugs.

A List of Drugs in Development for Neurodegenerative Diseases [PDF] compiled by Myoung-Ok Kwon and colleagues (2004) is available from the journal Neurodegenerative Diseases; 1(2-3):113–152.

Please support the NIMH's GenRED (Genetics of Recurrent Early-onset Depression) study, the largest psychiatric genetics study ever attempted.

Updated 12/03/07

Treatments for Depression and Anxiety

Drug Name Pharmacologic Action Company Indication Developmen Links tal Phase Pristiq (DVS- Metabolite of Effexor Wyeth Depression, Approvable 233 SR, () anxiety (but further needed ) Phase III trials suggest a 2008 approval date) Gepirone ER 5-HT1A partial Fabre- Depression, Not [Fabre- Kramer anxiety Approvable Kramer's Drug Profile] (SR NK2 antagonist Sanofi- Depression, Phase III [Effects of SR 48968) Aventis anxiety 48968 on rodents] Valdoxan 5-HT2C antagonist, 5-HT2B Servier, Depression, EU: [ (, antagonist, melatonin M1/M2 Novartis anxiety, Resubmissio activity] [Oct AGO 178) receptor agonist sleep n planned in 2005 press disorders ’07. US: release] Phase III Amibegron, SR beta-3-adrenoceptor agonist Sanofi- Depression, A [SR 58611 is 58611 Aventis anxiety supplement a selective al NDA is beta-3- possible in adrenoceptor 2007 agonist] 5-HT1A partial agonist, Clinical Data Depression Phase III [January serotonin Online, Inc. 2007 Press Release] , CRF1 antagonist Bristol-Myers Depression, Phase III BMS-562086 Squibb anxiety Lu AA21004 bis-aryl-sulphanyl modulator Lundbeck Depression, Phase II anxiety , NK1 antagonist GSK Depression, Phase II GW679769 anxiety, emesis PRX-00023 5-HT1A agonist, sigma Epix Depression Phase II [Compound Profile] Miraxion, LAX- "Purified" Omega-3 [EPA] Amarin Huntington' Phase II 101 s Disease, Depression TIK-101 NMDA Antagonist Tikvah Anxiety Phase II Pharmaceuti cals TGWOOAD/AA 5-HT1A agonist, 5-HT2 Fabre- Anxiety Phase II [Fabre- antagonist Kramer Kramer's info] TGBA01AD Serotonin reuptake inhibitor, Fabre- Depression Phase II [Fabre- 5-HT2 agonist, 5-HT1A Kramer Kramer's agonist, and 5-HT1D agonist info] GW372475, Dopamine, serotonin, and GSK, Depression Phase II NS2359 norepinephrine, reuptake NeuroSearch inhibitor Nemifitide Pentapeptide analog of Tetragenex Depression Phase II [Innapharma' (INN 00835) melanocyte-inhibiting factor s info] (MIF-1) administered [Antidepressa intravenously (mechanism nt-like effects unknown) of a novel pentapeptide , nemifitide, in an animal model of depression] [MIF-1 may regulate ACTH secretion] ORG GR antagonist Organon Depression Phase II 34517/34850 , NK1 antagonist GSK Depression, Phase II GW597599 anxiety DOV 21, 947 Dopamine, serotonin, and DOV/Merck Depression, Phase II [Antidepressa norepinephrine, reuptake ADHD, RLS nt-like inhibitor actions of DOV 21,947] LY2216684 Norepinephrine reuptake Eli Lilly Depression, Phase II inhibitor ADHD YKP-10A, Phenylalanine derivative with Janssen Depression Phase II [First Phase II R228060 unknown mechanism (Johnson & Study] Johnson)/SK Pharmaceuti cals PD 332-334 Alpha2delta calcium channel Pfizer Anxiety Phase II [11/06 Pfizer blocker Presentation] Elzasonan, CP- 5-HT1B and 5-HT1D receptor Pfizer Depression, Phase II 448,187 antagonist anxiety Lu AA24530 Multiple targets Lundbeck Depression, Phase II anxiety SEP-225289 DA/NE/5-HT reuptake Sepracor Depression, Phase I inhibitor anxiety SSR149415 V1B antagonist Sanofi- Depression, Phase II [SSR149415 Aventis anxiety, review] hyperphagi a AZD6765 - AstraZeneca Depression, Phase II anxiety GW876008 CRF1 antagonist Neurocrine/G Depression, Phase II SK anxiety, IBS ONO-2333Ms CRF1 antagonist Ono Depression, Phase II Pharmaceuti anxiety cals R-tofisopam R-isomer of racemic Pharmos Anxiety, IBS Phase I tofisopam (a 2,3- benzodiazepine) GW823296 NK1 antagonist GSK Depression, Phase I (orvepitant) anxiety Tyrima Reversible monoamine CeNeRx Depression, Phase I oxidase A (MAO-A) inhibitor anxiety PRE703 MgluR agonist Prescient Anxiety Phase I Delucemine, NMDA antagonist NPS Depression, Phase I [NPS-1506 NPS 1506 stroke provides neuroprotecti on] Lu AA34893 Lundbeck Depression, Phase I anxiety Lu AA44608 receptor Lundbeck Depression, Phase I antagonist anxiety AFQ056 mGluR5 receptor antagonist Novartis Anxiety Phase I JNJ-19567470 CRF1 antagonist Janssen Depression, Phase I or TS-041 (Johnson & anxiety Johnson), Taisho SSR 125543 CRF1 antagonist Sanofi- Depression, Phase I Aventis anxiety, hyperphagi a YKP3089 Undisclosed mechanism of SK Anxiety Phase I action Pharmaceuti cals

163090 Mixed serotonin receptor GSK Depression, Phase I agonist anxiety TC-2216 Nicotinic acetylcholine Targacept Depression Phase I receptor (alpha4beta2) antagonist TC-5214 Nonselective Nicotinic Targacept Depression Phase I acetylcholine receptor antagonist AZD2327 Enkephalinergic modulator AstraZeneca Anxiety Phase I R1647 Roche Depression, Phase I anxiety URB597 FAAH (fatty acid amide Organon Depression Phase II hydrolase) inhibitor -- CRF1 antagonist Neurogen Depression, Pre-clinical anxiety SSR 126374 CRF1 antagonist Sanofi- Depression, Pre-clinical Aventis anxiety, hyperphagi a SSR 411298 FAAH (fatty acid amide Sanofi- Depression, Pre-clinical hydrolase) inhibitor Aventis anxiety, hyperphagi a CRF1 CRF1 antagonist GSK/Neurocri Depression, Pre-clinical antagonist ne anxiety (backup) R1661 Roche Anxiety Pre-clinical SAR 102279 NK2 receptor antagonist Sanofi- Depression, Pre-clinical Aventis anxiety YKP581 Undisclosed mechanism of SK Depression Pre-clinical action Pharmaceuti cals (J & J)

Treatments for Sleep Disorders

Drug Name Pharmacologic Action Company Indication Developmen Links tal Phase Indiplon IR; GABA-A modulator (at BZ1 Neurocrine Sleep FDA decision [Neurocrin Indiplon MR sites) disorders expected by e's info] December 12, 2007 Eplivanserin, 5-HT2A receptor antagonist Sanofi- Sleep Phase III SR 46349 Aventis disorders Silenor is a potent Somaxon Sleep Phase III [Somaxon' (doxepin) antagonist at histamine H1 disorders s info] and H2 receptors. It may weakly inhibit the reuptake of norepinephrine and serotonin. Doxepin is also an antagonist at alpha-1-adrenoceptors. The drug binds to both serotonin 5-HT2A and 5-HT2C receptors. In addition, it is an antagonist at all subtypes of muscarinic acetylcholine receptors (references provided elsewhere). VEC-162 Melatonin receptor agonist Vanda Sleep Phase III [Vanda's Pharmaceutic disorders, info] als depression ORG 50081 5-HT2 antagonist, H1 Organon Sleep Phase III antagonist, alpha-2- disorders, adrenoceptor antagonist hot flashes Volinanserin, M- 5-HT2A antagonist Sanofi- Sleep Phase III [M-100907 100907 Aventis disorders review] APD125 5-HT2A inverse agonist Arena Sleep Phase III disorders Adipiplon, NG2- GABA-A modulator Neurogen Sleep Phase III 73 disorders PD-6735 Melatonin receptor agonist Phase 2 Sleep Phase II Discovery Disorders Pruvanserin, 5-HT2A antagonist Eli Lilly Sleep Phase II EMD 281014 disorders Pimavanserin, Serotonin 5-HT2A receptor Acadia Sleep Phase II [June 07 ACP-103 inverse agonist, dopamine disorders, Press D2/D3 receptor partial Parkinson's Release] agonist, acetylcholine M1 disease receptor agonist psychosis, schizophreni a co-therapy PD 200-390 Alpha2delta calcium channel Pfizer Sleep Phase II [11/06 blocker disorders Pfizer Presentati on] HY10275 5-HT2A and histamine H1 Eli Lilly Depression, Phase II receptor antagonist ADHD TIK-301, Melatonin agonist, 5-HT2B/5- Tikvah Sleep Phase II LY156735 HT2C antagonist Pharmaceutic disorders als GW649868 antagonist GSK Sleep Phase II disorders , Orexen OX1 and OX2 receptor Actelion Sleep Phase II [Actelion's ACT-078573 antagonist disorders Web Site] PD-200,390 Voltage-gated calcium Pfizer Sleep Phase II channel alpha(2)delta subunit disorders modulator AVE 8488 5-HT2A antagonist Sanofi- Sleep Pre-clinical Aventis disorders

Treatments for Psychosis/Bipolar Disorder

Drug Name Pharmacologic Action Company Indication Development Links al Phase Invega Full 5-HT2/partial D2 Johnson & Psychosis Approved (Paliperidone antagonist with high affinity Johnson IM, ER) for 5-HT7 receptors. Active metabolite of Risperdal Bifeprunox (DU- Partial agonist at dopamine Solvay, Psychosis Not 127090) D2 and serotonin 5-HT1A Wyeth approvable receptors Zomaril Selective DA/NE/5-HT Vanda Psychosis NDA (Iloperidone) antagonist Pharmaceutic Submitted als Corlux (AKA Glucocorticoid receptor type II Corcept Psychosis, Phase III, [Corcept mifepristone or (GRII) antagonist, depression granted fast- 's info] RU-486) receptor track status antagonist by the FDA Asenapine (ORG 5-HT2 antagonist, D2 partial Organon Psychosis Phase III [Organo 5222) agonist n 2003 press release] Ocaperidone D2/5-HT2 antagonist Neuro3d, Psychosis Phase III Drug Janssen profile SLV 308 D2 partial agonist, 5-HT1A Solvay Psychosis, Phase III agonist Parkinson's disease LIC477D Voltage-gated sodium channel Novartis Psychosis Phase III (licarbazepine) inhibitor Pimavanserin, Serotonin 5-HT2A receptor Acadia Antipsychoti Phase III [June 07 ACP-103 inverse agonist, dopamine c-induced Press D2/D3 receptor partial side effects, Release] agonist, acetylcholine M1 Parkinson's receptor agonist disease psychosis ORG Glucocorticoid receptor type II Organon Depression, Phase II 34517/34850 (GRII) antagonist psychosis ORG 24448 AMPA modulator Organon/Cort Psychosis Phase II ex ACP-104 Metabolite of clozapine Acadia Psychosis Phase II RG2133 Prodrug of uridine Repligen Bipolar Phase II [Replige (triacetyluridine disorder n's info] ) [10/21/0 5 press release] Lonasen D2, 5-HT2A antagonist Dainippon Psychosis Phase II (blonanserin) Sumitomo LY2140023 Prodrug for an mGluR2/3 Eli Lilly Psychosis Phase II agonist Mirapex Dopamine D2, D3 receptor Boehringer- Bipolar Phase II (pramipexole) agonist Ingelheim Disorder Lu-35-138 D4/5-HT antagonist Lundbeck Psychosis Phase II (SM D2, 5-HT2A antagonist Merck, Psychosis Phase II 13496) Dainippon Sumitomo (SB- NK-3 antagonist GSK Psychosis, Phase II 223412) IBS, overactive bladder AVE 1625 CB1 antagonist Sanofi-Aventis Psychosis Phase II P-101 Alpha-2-adrenoceptor Potomac Schizophreni Phase II antagonist Pharma a ORG 25935 GLYT1 (glycine transporter) Organon Psychosis Phase II inhibitor RG1068, Endogenous pancreatic Repligen Psychosis, Phase II hormone autism, anxiety SLV 310,313 5-HT2A antagonist Solvay Psychosis Phase II SSR 181507 D2/5-HT2 antagonist Sanofi-Aventis Psychosis Phase I ABT-089 Nicotinic acetylcholine Abbott Psychosis, Phase I receptor agonist Laboratories ADHD GW742457 5-HT6 antagonist GSK Psychosis, Phase I Alzheimer's disease GW773812 D2, 5-HT antagonist GSK Psychosis Phase I TC-1827 Selective alpha4beta2 Targacept Cognitive Phase I nicotinic acetylcholine impairment receptor agonist associated with schizophreni a YKP 1538 SK Psychosis Phase I Pharmaceutic als SSR 125047 Sigma receptor antagonist Sanofi-Aventis Psychosis Phase I SSR 504734 GLYT1 (Type 1 glycine Sanofi-Aventis Psychosis Phase I transporter) inhibitor JNJ-17305600 GLYT1 inhibitor Johnson & Psychosis Phase I Johnson XY 2401 Glycine site specific NMDA Xytis Psychosis Phase I modulator PNU 170413 Pfizer Psychosis Phase I RGH-188 D2, D3 antagonist Forrest Psychosis Phase I PDE10A PDE10A inhibitor Memory Psychosis Preclinical Pharm./ Roche SSR 180711 alpha7 nicotinic acetylcholine Sanofi-Aventis Psychosis Preclinical receptor partial agonist SSR 103800 GLYT1 (Type 1 glycine Sanofi-Aventis Psychosis Preclinical transporter) inhibitor SSR 241586 NK3 antagonist Sanofi-Aventis Psychosis Preclinical Treatments for Attention Deficit Hyperactivity Disorder (ADHD)

Drug Name Pharmacologic Action Company Indication Development Links al Phase Vyvanse Amphetamine conjugated to a Shire ADHD Approved [New specific amino acid Pharmaceutic River als/ New compou River nd info] Pharmaceutic als SPD-465 (longer Long-acting amphetamine Shire ADHD Approvable, acting Adderall product Pharmaceutic awaiting XR) als final FDA approval Intuniv (SPD- Alpha-2A-adrenoceptor Shire ADHD Approvable, 503, agonist Pharmaceutic awaiting guanfacine) als final FDA approval CX-717 AMPA Cortex ADHD The FDA has Pharmaceutic rejected the als request for the ADHD indication... Will not pursue Altropane Highly selective dopamine Boston Life ADHD Phase II transporter radioligand Sciences ABT-089 Nicotinic acetylcholine Abbott ADHD, Phase II receptor agonist Laboratories Psychosis ABT-894 Nicotinic acetylcholine Abbott ADHD Phase II receptor agonist Laboratories PF-03654746 Pfizer ADHD Phase II MEM3454 Alpha-7 nicotinic acetylcholine Memory ADHD Phase II [Memor receptor partial agonist Pharm./ y's drug Roche profile] DOV-102,677 DA/NE/5-HT reuptake inhibitor DOV ADHD Phase I (with preferential action on Pharmaceutic the dopamine transporter) als SON-216 Sosei ADHD Phase I () SPD-483 ATS (Amphetamine Shire ADHD Preclinical Transdermal System) Pharmaceutic als

APPENDIX: Glossary

Phase I: Phase I includes the initial introduction of an investigational new drug into humans. Phase I studies are typically closely monitored and may be conducted in patients or normal volunteer subjects. These studies are designed to determine the metabolism and pharmacologic actions of the drug in humans, the side effects associated with increasing doses, and, if possible, to gain early evidence on effectiveness. During Phase I, sufficient information about the drug's and pharmacological effects should be obtained to permit the design of well-controlled, scientifically valid, Phase II studies. The total number of subjects and patients included in Phase I studies varies with the drug, but is generally in the range of 20 to 80.

Phase II: Phase II includes the controlled clinical studies conducted to evaluate the effectiveness of the drug for a particular indication or indications in patients with the disease or condition under study and to determine the common short-term side effects and risks associated with the drug. Phase II studies are typically well controlled, closely monitored, and conducted in a relatively small number of patients, usually involving no more than several hundred subjects.

Phase III: A phase III trial frequently compares a new treatment to a standard treatment or to no treatment, and treatment allocation may be randomly assigned and the data masked. These studies usually involve a large number of participants followed for longer periods of treatment exposure. Phase III studies are expanded controlled and uncontrolled trials. Phase III studies usually include from several hundred to several thousand subjects.

NDA: New Drug Application. NDA refers to the data that the drug company submits to the FDA at the time of the drug's application filing.

Approvable: Term giving to a drug's approval status by the FDA. Before the drug can be launched, the company has to fulfill ongoing clinical and manufacturing concerns brought up by the FDA.