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

This list was graciously provided by JR Becker (jrbecker76@hotmail.com). Some additions have been made by Shawn Thomas (shawn@neurotransmitter.net). Please send additions or corrections to jrbecker76@hotmail.com

Information about recent drug approvals can be obtained from the FDA Center for Drug Evaluation and Research. For information about drugs 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 Developmental Phase

Links

Pristiq (DVS-233 SR, desvenlafaxine)

Metabolite of Effexor (venlafaxine) Wyeth Depression, anxiety

Approvable (but further needed Phase III trials suggest a 2008 approval date)

Gepirone ER 5-HT1A partial agonist Fabre-Kramer Depression, anxiety

Not Approvable [Fabre-Kramer's Drug Profile]

Saredutant (SR 48968)

NK2 antagonist Sanofi-Aventis Depression, anxiety

Phase III [Effects of SR 48968 on rodents]

Valdoxan (agomelatine, AGO 178)

5-HT2C antagonist, 5-HT2B antagonist, melatonin M1/M2 receptor agonist

Servier, Novartis

Depression, anxiety, sleep disorders

EU: Resubmission planned in ’07. US: Phase III

[Receptor activity] [Oct 2005 press release]

Amibegron, SR 58611

beta-3-adrenoceptor agonist Sanofi-Aventis Depression, anxiety

A supplemental NDA is possible in 2007

[SR 58611 is a selective beta-3-adrenoceptor agonist]

Vilazodone 5-HT1A partial agonist, serotonin reuptake inhibitor

Clinical Data Online, Inc.

Depression Phase III [January 2007 Press Release]

Pexacerfont, BMS-562086

CRF1 antagonist Bristol-Myers Squibb

Depression, anxiety

Phase III

Lu AA21004 bis-aryl-sulphanyl modulator Lundbeck Depression, anxiety

Phase II

Casopitant, GW679769

NK1 antagonist GSK Depression, anxiety, emesis

Phase II

PRX-00023 5-HT1A agonist, sigma receptor antagonist

Epix Depression Phase II [Compound Profile]

Miraxion, LAX-101 "Purified" Omega-3 [EPA] Amarin Huntington's Disease, Depression

Phase II

TIK-101 NMDA Antagonist Tikvah Pharmaceuticals

Anxiety Phase II

TGWOOAD/AA 5-HT1A agonist, 5-HT2 antagonist Fabre-Kramer Anxiety Phase II [Fabre-Kramer's info]

TGBA01AD Serotonin reuptake inhibitor, 5-HT2 agonist, 5-HT1A agonist, and 5-HT1D agonist

Fabre-Kramer Depression Phase II [Fabre-Kramer's info]

GW372475, NS2359

Dopamine, serotonin, and norepinephrine, reuptake inhibitor

GSK, NeuroSearch

Depression Phase II

Nemifitide (INN 00835)

Pentapeptide analog of melanocyte-inhibiting factor (MIF-1) administered intravenously (mechanism unknown)

Tetragenex Depression Phase II [Innapharma's info] [Antidepressant-like effects of a novel pentapeptide, nemifitide, in an animal model of depression] [MIF-1 may regulate ACTH secretion]

ORG 34517/34850 GR antagonist Organon Depression Phase II

Vestipitant, GW597599

NK1 antagonist GSK Depression, anxiety

Phase II

DOV 21, 947 Dopamine, serotonin, and norepinephrine, reuptake inhibitor

DOV/Merck Depression, ADHD, RLS

Phase II [Antidepressant-like actions of DOV 21,947]

LY2216684 Norepinephrine reuptake inhibitor Eli Lilly Depression, ADHD

Phase II

YKP-10A, R228060 Phenylalanine derivative with unknown mechanism

Janssen (Johnson & Johnson)/SK Pharmaceuticals

Depression Phase II [First Phase II Study]

PD 332-334 Alpha2delta calcium channel blocker

Pfizer Anxiety Phase II [11/06 Pfizer Presentation]

Elzasonan, CP-448,187

5-HT1B and 5-HT1D receptor antagonist

Pfizer Depression, anxiety

Phase II

Lu AA24530 Multiple targets Lundbeck Depression, anxiety

Phase II

SEP-225289 DA/NE/5-HT reuptake inhibitor Sepracor Depression, anxiety

Phase I

SSR149415 V1B antagonist Sanofi-Aventis Depression, anxiety, hyperphagia

Phase II [SSR149415 review]

AZD6765 - AstraZeneca Depression, anxiety

Phase II

GW876008 CRF1 antagonist Neurocrine/GSK

Depression, anxiety, IBS

Phase II

ONO-2333Ms CRF1 antagonist Ono Pharmaceuticals

Depression, anxiety

Phase II

R-tofisopam R-isomer of racemic tofisopam (a 2,3-benzodiazepine)

Pharmos Anxiety, IBS Phase I

GW823296 (orvepitant)

NK1 antagonist GSK Depression, anxiety

Phase I

Tyrima Reversible monoamine oxidase A (MAO-A) inhibitor

CeNeRx Depression, anxiety

Phase I

PRE703 MgluR agonist Prescient Anxiety Phase I Delucemine, NPS 1506

NMDA antagonist NPS Depression, stroke

Phase I [NPS-1506 provides neuroprotection]

Lu AA34893 Lundbeck Depression, anxiety

Phase I

Lu AA44608 Neuropeptide Y receptor antagonist

Lundbeck Depression, anxiety

Phase I

AFQ056 mGluR5 receptor antagonist Novartis Anxiety Phase I JNJ-19567470 or TS-041

CRF1 antagonist Janssen (Johnson & Johnson), Taisho

Depression, anxiety

Phase I

SSR 125543 CRF1 antagonist Sanofi-Aventis Depression, anxiety, hyperphagia

Phase I

YKP3089 Undisclosed mechanism of action SK Pharmaceuticals

Anxiety Phase I

163090 Mixed serotonin receptor agonist GSK Depression,

anxietyPhase I

TC-2216 Nicotinic acetylcholine receptor (alpha4beta2) antagonist

Targacept Depression Phase I

TC-5214 Nonselective Nicotinic acetylcholine receptor antagonist

Targacept Depression Phase I

AZD2327 Enkephalinergic modulator AstraZeneca Anxiety Phase I R1647 Roche Depression,

anxietyPhase I

URB597 FAAH (fatty acid amide hydrolase) inhibitor

Organon Depression Phase II

-- CRF1 antagonist Neurogen Depression, anxiety

Pre-clinical

SSR 126374 CRF1 antagonist Sanofi-Aventis Depression, anxiety, hyperphagia

Pre-clinical

SSR 411298 FAAH (fatty acid amide hydrolase) inhibitor

Sanofi-Aventis Depression, anxiety, hyperphagia

Pre-clinical

CRF1 antagonist (backup)

CRF1 antagonist GSK/Neurocrine

Depression, anxiety

Pre-clinical

R1661 Roche Anxiety Pre-clinical SAR 102279 NK2 receptor antagonist Sanofi-Aventis Depression,

anxiety Pre-clinical

YKP581 Undisclosed mechanism of action SK Pharmaceuticals (J & J)

Depression Pre-clinical

Treatments for Sleep Disorders

Drug Name Pharmacologic Action Company Indication Developmental Phase

Links

Indiplon IR; Indiplon MR

GABA-A modulator (at BZ1 sites) Neurocrine Sleep disorders FDA decision expected by December 12, 2007

[Neurocrine's info]

Eplivanserin, SR 46349

5-HT2A receptor antagonist Sanofi-Aventis Sleep disorders Phase III

Silenor (doxepin) Doxepin is a potent antagonist at histamine H1 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).

Somaxon Sleep disorders Phase III [Somaxon's info]

VEC-162 Melatonin receptor agonist Vanda Pharmaceuticals

Sleep disorders, depression

Phase III [Vanda's info]

ORG 50081 5-HT2 antagonist, H1 antagonist, alpha-2-adrenoceptor antagonist

Organon Sleep disorders, hot flashes

Phase III

Volinanserin, M-100907

5-HT2A antagonist Sanofi-Aventis Sleep disorders Phase III [M-100907 review]

APD125 5-HT2A inverse agonist Arena Sleep disorders Phase III Adipiplon, NG2-73 GABA-A modulator Neurogen Sleep disorders Phase III PD-6735 Melatonin receptor agonist Phase 2

Discovery Sleep Disorders

Phase II

Pruvanserin, EMD 281014

5-HT2A antagonist Eli Lilly Sleep disorders Phase II

Pimavanserin, ACP-103

Serotonin 5-HT2A receptor inverse agonist, dopamine D2/D3 receptor partial agonist, acetylcholine M1 receptor agonist

Acadia Sleep disorders, Parkinson's disease psychosis, schizophrenia co-therapy

Phase II [June 07 Press Release]

PD 200-390 Alpha2delta calcium channel blocker

Pfizer Sleep disorders Phase II [11/06 Pfizer Presentation]

HY10275 5-HT2A and histamine H1 receptor antagonist

Eli Lilly Depression, ADHD

Phase II

TIK-301, LY156735 Melatonin agonist, 5-HT2B/5-HT2C antagonist

Tikvah Pharmaceuticals

Sleep disorders Phase II

GW649868 Orexin antagonist GSK Sleep disorders Phase II Almorexant, ACT-078573

Orexen OX1 and OX2 receptor antagonist

Actelion Sleep disorders Phase II [Actelion's Web Site]

PD-200,390 Voltage-gated calcium channel alpha(2)delta subunit modulator

Pfizer Sleep disorders Phase II

AVE 8488 5-HT2A antagonist Sanofi-Aventis Sleep disorders Pre-clinical

Treatments for Psychosis/Bipolar Disorder

Drug Name Pharmacologic Action Company Indication Developmental Phase

Links

Invega (Paliperidone IM, ER)

Full 5-HT2/partial D2 antagonist with high affinity for 5-HT7 receptors. Active metabolite of Risperdal

Johnson & Johnson

Psychosis Approved

Bifeprunox (DU-127090)

Partial agonist at dopamine D2 and serotonin 5-HT1A receptors

Solvay, Wyeth Psychosis Not approvable

Zomaril (Iloperidone)

Selective DA/NE/5-HT antagonist Vanda Pharmaceuticals

Psychosis NDA Submitted

Corlux (AKA mifepristone or RU-486)

Glucocorticoid receptor type II (GRII) antagonist, progesterone receptor antagonist

Corcept Psychosis, depression

Phase III, granted fast-track status by the FDA

[Corcept's info]

Asenapine (ORG 5222)

5-HT2 antagonist, D2 partial agonist Organon Psychosis Phase III [Organon 2003 press release]

Ocaperidone D2/5-HT2 antagonist Neuro3d, Janssen

Psychosis Phase III Drug profile

SLV 308 D2 partial agonist, 5-HT1A agonist Solvay Psychosis, Parkinson's disease

Phase III

LIC477D (licarbazepine)

Voltage-gated sodium channel inhibitor

Novartis Psychosis Phase III

Pimavanserin, ACP-103

Serotonin 5-HT2A receptor inverse agonist, dopamine D2/D3 receptor partial agonist, acetylcholine M1 receptor agonist

Acadia Antipsychotic-induced side effects, Parkinson's disease psychosis

Phase III [June 07 Press Release]

ORG 34517/34850 Glucocorticoid receptor type II (GRII) antagonist

Organon Depression, psychosis

Phase II

ORG 24448 AMPA modulator Organon/Cortex Psychosis Phase II ACP-104 Metabolite of clozapine Acadia Psychosis Phase II RG2133 (triacetyluridine)

Prodrug of uridine Repligen Bipolar disorder

Phase II [Repligen's info] [10/21/05 press release]

Lonasen (blonanserin)

D2, 5-HT2A antagonist Dainippon Sumitomo

Psychosis Phase II

LY2140023 Prodrug for an mGluR2/3 agonist Eli Lilly Psychosis Phase II Mirapex (pramipexole)

Dopamine D2, D3 receptor agonist Boehringer-Ingelheim

Bipolar Disorder

Phase II

Lu-35-138 D4/5-HT antagonist Lundbeck Psychosis Phase II Lurasidone (SM 13496)

D2, 5-HT2A antagonist Merck, Dainippon Sumitomo

Psychosis Phase II

Talnetant (SB-223412)

NK-3 antagonist GSK Psychosis, IBS, overactive bladder

Phase II

AVE 1625 CB1 antagonist Sanofi-Aventis Psychosis Phase II P-101 Alpha-2-adrenoceptor antagonist Potomac Pharma Schizophrenia Phase II

ORG 25935 GLYT1 (glycine transporter) inhibitor Organon Psychosis Phase II

RG1068, secretin Endogenous pancreatic hormone Repligen Psychosis, autism, anxiety

Phase II

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 receptor

agonist Abbott Laboratories

Psychosis, ADHD

Phase I

GW742457 5-HT6 antagonist GSK Psychosis, Alzheimer's disease

Phase I

GW773812 D2, 5-HT antagonist GSK Psychosis Phase I TC-1827 Selective alpha4beta2 nicotinic

acetylcholine receptor agonistTargacept Cognitive

impairment associated with schizophrenia

Phase I

YKP 1538 SK Pharmaceuticals

Psychosis Phase I

SSR 125047 Sigma receptor antagonist Sanofi-Aventis Psychosis Phase I SSR 504734 GLYT1 (Type 1 glycine transporter)

inhibitor Sanofi-Aventis Psychosis Phase I

JNJ-17305600 GLYT1 inhibitor Johnson & Johnson

Psychosis Phase I

XY 2401 Glycine site specific NMDA modulator

Xytis Psychosis Phase I

PNU 170413 Pfizer Psychosis Phase I RGH-188 D2, D3 antagonist Forrest Psychosis Phase I PDE10A PDE10A inhibitor Memory Pharm./

RochePsychosis Preclinical

SSR 180711 alpha7 nicotinic acetylcholine receptor partial agonist

Sanofi-Aventis Psychosis Preclinical

SSR 103800 GLYT1 (Type 1 glycine transporter) inhibitor

Sanofi-Aventis Psychosis Preclinical

SSR 241586 NK3 antagonist Sanofi-Aventis Psychosis Preclinical

Treatments for Attention Deficit Hyperactivity Disorder (ADHD)

Drug Name Pharmacologic Action Company Indication Developmental Phase

Links

Vyvanse Amphetamine conjugated to a specific amino acid

Shire Pharmaceuticals/ New River Pharmaceuticals

ADHD Approved [New River compound info]

SPD-465 (longer acting Adderall XR)

Long-acting amphetamine product Shire Pharmaceuticals

ADHD Approvable, awaiting final FDA approval

Intuniv (SPD-503, guanfacine)

Alpha-2A-adrenoceptor agonist Shire Pharmaceuticals

ADHD Approvable, awaiting final FDA approval

CX-717 AMPA receptor modulator Cortex ADHD The FDA has

Pharmaceuticals rejected the request for the ADHD indication... Will not pursue

Altropane Highly selective dopamine transporter radioligand

Boston Life Sciences

ADHD Phase II

ABT-089 Nicotinic acetylcholine receptor agonist

Abbott Laboratories

ADHD, Psychosis

Phase II

ABT-894 Nicotinic acetylcholine receptor agonist

Abbott Laboratories

ADHD Phase II

PF-03654746 Pfizer ADHD Phase II MEM3454 Alpha-7 nicotinic acetylcholine

receptor partial agonist Memory Pharm./ Roche

ADHD Phase II [Memory's drug profile]

DOV-102,677 DA/NE/5-HT reuptake inhibitor (with preferential action on the dopamine transporter)

DOV Pharmaceuticals

ADHD Phase I

SON-216 (bifemelane)

Sosei ADHD Phase I

SPD-483 ATS (Amphetamine Transdermal System)

Shire Pharmaceuticals

ADHD Preclinical

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 pharmacokinetics 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.