This is a list of investigational aggression drugs, or drugs that are currently under development for clinical use in the treatment of aggression but are not yet approved. Drugs used to treat aggression may also be known as "serenics". [1]
Chemical/generic names are listed first, with developmental code names, synonyms, and brand names in parentheses.
This list was last comprehensively updated in February 2025. It is likely to become outdated with time.
The early serenics (fluprazine, DU28412, DU 27725, eltoprazine, batoprazine: Olivier et al. (1990a,b)) are mixed 5- HT1A/1B receptor agonist, leaving the 5-HT1A receptor still as an option for mediating (part of) the anti-aggressive effect, but more recently synthesized 5-HT1B receptor agonists including, e.g. anpirtoline, CP-94,253 (5-propoxy-3-( 1,2,3,6- tetrahydro4-pyridinyl)-1H-pyrrolo[3,2-b]pyridine) and zolmitriptan, are far more selective for this receptor and showed a similar, highly specific anti-aggressive effect, both in aggressive residential mice and in mice made more aggressive via low-doses of alcohol or social instigation (Fish et al., 1999; de Almeida et al., 2001; De Almeida and Miczek, 2002; Miczek and de Almeida, 2001). [...]
Along 1993-98, our group conducted a pilot, randomiz-ed, triple-blind, head-to-head, parallel-group clinical trial,to examine the effectiveness and safety of cyproterone against haloperidol in the treatment of aggression associa-ted with Alzheimer's dementia5. Cyproterone proved to be significantly more effective and better tolerated than haloperidol as a specific antiaggressive treatment in this population (report in preparation).
Several other medications are being used in treatment of aggression, but less commonly than those mentioned above. Medroxyprogesterone is an anti-androgen which lowers testosterone. It is the equivalent of a pharmacological castration and will decrease or eliminate the sex drive in males. [...] The correlation between androgens and violence is not entirely clear; Virkkunen and Linnoila (1993) report, for instance, that testosterone levels are associated with outward-directed aggressiveness and lack of socialization as opposed to impulsiveness. The use of anti-androgens also presents certain ethical questions, such as whether it could be said to be freely chosen when a jail sentence is a potential alternative or whether it should even be offered as an allowable alternative. The treatment is controversial and ethical guidelines have not been established.
Cyproterone acetate, medroxyprogesterone acetate, leuprolide acetate and spironolactone are anti-androgen drugs used when there are indications of hyperandrogeny. [...] These medications have also been used in the treatment of aggression in various clinical populations: sexual offenders, demented aggressive patients, aggressive patients with brain injuries, children with precocious puberty, and children with ASD (Bradstreet et al. 2007; Caparros-Lefebvre & Dewailly 2005; Huertas et al. 2007; Laue & Cutler 1994; Leschek et al. 1999; O'Connor & Baker 1983). Anti-androgen medication may prove a valuable adjunctive treatment to behavioral interventions and reduce the intensity and duration of aggressive episodes in individuals with explosive aggression and ASD. Although existing evidence for the therapeutic effects of anti-androgen medication is promising, there are no randomized controlled trials with most research involving uncontrolled case studies or open trials conducted mainly in populations others than children with autism. Some reports are anecdotal findings of reduced aggression during primary treatment of other diseases with anti-androgen medication (e.g. precocious puberty) (Laue & Cutler 1994; Leschek et al. 1999). [...] Research investigating hormonal levels in ASD children and objective assessment of aggressive behavior are essential for further potential clinical indications for anti-androgen therapy.
Using such an ethopharmacological approach in either rats or mice, it has recently been claimed that only certain specific 5-HT1A receptor agonists (i.e., alnespirone and S-15535; de Boer et al., 1999, 2000), a mixed 5-HT1A/1B receptor agonist (i.e., eltoprazine; Olivier et al., 1995) and several specific 5-HT1B receptor agonists (i.e., CGS12066b, CP-94,253, anpirtoline, zolmitriptan, sumatriptan; Bell and Hobson, 1994; Fish et al., 1999; De Almeida et al., 2001; Miczek et al., 2004) exert behavioral specific anti-aggressive effects. In particular, it was claimed that agonists acting on the 5-HT1B receptors have more selective anti-aggressive effects in mice than those acting on 5-HT1A receptors (Miczek et al., 2004; Olivier, 2004).
There are a few currently available data in support of the antiaggressive role of 5-HT2C receptors: (1) the activation of 5-HT2C receptors enhanced the display of defeat submissive and defensive behavior in golden hamsters [172]. (2) 5-HT2C receptor agonist/alpha 2 receptor antagonist S32212 suppressed aggressive behavior in mice [173]. (3) Mice expressing only the VGV isoform of 5-HT2C receptors displayed a high level of conspecific aggression [174]. (4) The association between Htr2c gene polymorphism and criminal behavior in humans was demonstrated [175]. (5) Recently, a novel 5-HT2C agonist, lorcaserin, has been demonstrated to have antiaggressive properties in human subjects with impulsive aggressive behavior. Lorcaserin attenuated provoked, but not unprovoked, aggression in impulsively aggressive individuals indicating that 5-HT2C receptor may be a putative target for the treatment of impulsive aggressive behavior in human subjects [176].
Based on evidence from a recent pilot study, lorcaserin, a selective 5-HT2c agonist, was found to have anti-aggressive effects in humans with high levels of impulsive aggression like in those diagnosed with IED.