In recent years, the goals of treatment in schizophrenia have evolved from objective improvements in psychotic symptoms to encompass patient-related factors such as subjective response and quality of life. In order to examine factors that influence patient satisfaction with treatment, subjective quality of life and subjective response to treatment, two literature searches were performed using PubMed. The first searched for articles of any kind with no time limits using the search parameters ‘schizophrenia AND satisfaction’, ‘antipsychotic AND satisfaction’, ‘schizophrenia AND subjective response’, ‘schizophrenia AND therapeutic alliance’, ‘schizophrenia AND psychosocial OR psychoeducation’. Secondly, PubMed was searched between January 1990 and December 2005 using the key words ‘satisfaction’, ‘subjective response’ and ‘quality of life’ in combination with an array of atypical agents. Results demonstrated that patient satisfaction with antipsychotic therapy is influenced by multiple factors. The most frequently reported reasons for dissatisfaction include drug side effects, lack of involvement in treatment planning or decision-making and lack of involvement of family members in the care plan. The majority of studies have demonstrated that the atypical antipsychotics are associated with significant improvements in quality of life, functional status and patient satisfaction compared with conventional agents. The therapeutic alliance is key to achieving optimal outcomes, by providing information and education to meet patients’ needs, while facilitating compliance with drug therapy to ensure better clinical outcomes. A long-acting atypical antipsychotic that can ensure medication delivery will provide a platform for psychosocial interventions, and thus may further increase patient satisfaction and, ultimately, improve long-term outcomes in schizophrenia.

The negative symptoms of schizophrenia represent an impairment of normal emotional responses, thought processes and behaviors, and include blunting or flattening of affect, alogia/aprosody, avolition/apathy, anhedonia, and asociality. Negative symptoms contribute to a reduced quality of life, increased functional disability, increased burden of illness, and poorer long-term outcomes, to a greater degree than positive symptoms. Primary negative symptoms are prominent and persistent in up to 26% of patients with schizophrenia, and they are estimated to occur in up to 58% of outpatients at any given time. Negative symptoms respond less well to medications than positive symptoms, and to date treatment options for negative symptoms have been limited, with no accepted standard treatment. Modest benefits have been reported with a variety of different agents, including second-generation antipsychotics and add-on therapy with antidepressants and other pharmacological classes. Recent clinical research focusing on negative symptoms target novel biological systems, such as glutamatergic neurotransmission. Different approaches include: enhancing N-methyl-D-aspartate receptor function with agents that bind directly to the glycine ligand site or with glycine reuptake inhibitors; influencing the metabotropic glutamate receptor (mGluR2/3) with positive allosteric modulators; and stimulating nicotinic acetylcholine receptors. In conclusion, the lack of clearly efficacious pharmacological treatments for the management of negative symptoms represents a significant unmet need, especially considering the importance of these symptoms on patient outcomes. Hence, further research to identify and characterize novel pharmacological treatments for negative symptoms is greatly needed.

Risperidone long-acting injection (RLAI) was the first second-generation antipsychotic available as a long-acting injection. Paliperidone (9-hydroxyrisperidone) is the active metabolite of risperidone, introduced initially as an extended release oral (ORal Osmotic System, OROS®, Alza Corporation) formulation (Invega®, Janssen). Paliperidone long-acting injection (PLAI) has now been developed as a suspension of paliperidone palmitate nanocrystals in an aqueous formulation (Invega Sustenna®, Xeplion®), administered monthly by intramuscular injection (deltoid or gluteal). Doses of PLAI can be expressed either in milligram equivalents (mg eq) of paliperidone palmitate or in milligrams of the active fraction of paliperidone. The recommended initiation regimen of 150 mg eq (234 mg) on day 1 and 100 mg eq (156 mg) on day 8 (both administered in the deltoid) achieves therapeutic blood levels rapidly and without the necessity of oral supplementation. No refrigeration or reconstitution prior to administration is required. PLAI has been shown in to be effective in controlling the acute symptoms of schizophrenia as well as delaying time to relapse. Safety and tolerability are comparable to RLAI with no new safety signals. Thus, PLAI may represent the rational development of RLAI with greater ease of use.