Optimal pharmacotherapy for psychosis Unanswered questions include which antipsychotic medication should be the first line of therapy, what constitutes a sufficient period of time to determine whether a new medication is effective, how to handle poor response to the initial prescribed medication (Kane et al., 2003), and how the dosing of combination antipsychotics should be managed in the presence of increased symptoms or side effects. Moreover, multiple antipsychotic medications are used in the absence of evidence on their combined efficacy (Miller and Craig, 2002).

Medication treatments for certain substance dependencies No medications have yet shown effectiveness in the treatment of amphetamine or marijuana dependence.

The prevention and treatment of posttraumatic stress disorder (PTSD) Although PTSD has been recognized for centuries as a frequent consequence among those engaged in warfare (often under different names, such as “shell shock”), high rates of trauma and its adverse mental health sequelae also are experienced by significant portions of the general population—for example, as a result of childhood neglect and abuse; rape and other physical assaults or acts of personal violence; life-threatening or other serious accidents; and mass trauma affecting populations, such as through acts of terrorism, war, and natural disasters (Mueser et al., 2002; National Center for Post Traumatic Stress Disorder, 2005). Some types of psychotherapy (i.e., trauma-focused cognitive behavioral/exposure therapy for individuals and groups, and stress management) have been found to be effective in treating PTSD (Bisson and Andrew, 2005), as have some medications (Stein et al., 2005). Nonetheless, gaps remain in our knowledge of how to prevent PTSD from developing after trauma, what the risk factors are for PTSD (Rose et al., 2005; Work Group on ASD and PTSD, 2004), and how to treat the condition once it develops. With respect to treatment, for example, more knowledge is needed about what drugs and drug classes are most effective; which patients will respond best to medication (Stein et al., 2005); how best to combine pharmacotherapy and psychotherapy; and how to relieve some specific symptoms, such as insomnia or nightmares, by themselves and in the presence of other symptoms requiring medication (Work Group on ASD and PTSD, 2004). Moreover, although cognitive and behavioral therapies have demonstrated efficacy in treating victims of sexual assault, interpersonal violence, and industrial or vehicular accidents, their effectiveness in treating PTSD in combat veterans and victims of mass violence requires further study (Work Group on ASD and PTSD, 2004).

Therapies for high-prevalence childhood conditions While there has been an impressive increase in the number and quality of studies of effective

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