Improving treatment outcomes in schizophrenia: Looking beyond positive symptoms for early and effective intervention

Although the symptoms of schizophrenia are troublesome for almost all persons with the disease, its clinical presentation, and possibly also the underlying neurobiological pathology, vary among patients.

Moreover, a considerable number of patients do not experience satisfactory symptom resolution with antipsychotic medications and continue experiencing burdensome symptoms even after two or more lines of treatment. Negative symptoms and cognitive impairment - which tend to receive less treatment focus than the diagnostic positive symptoms - pose major challenges in the treatment of schizophrenia.

In this symposium, Prof Christoph Correll presented the current challenges and treatment strategies in the management of schizophrenia, focusing on the diversity in clinical presentation, disease trajectories, and outcomes among individuals with schizophrenia.


Opportunities and challenges in the treatment and prevention of positive symptoms

Professor Christoph Correll, Hofstra Northwell School of Medicine, USA, opened the session providing a status of the current treatment of schizophrenia focusing on positive symptoms. Although antipsychotics are better than placebo for treating positive symptoms, Prof Correll pointed out that about half of patients with acute schizophrenia still experience none or inadequate improvement with the currently available treatments.1 For approximately one-third of patients, inadequate response is seen even after complete treatment with two or more different antipsychotics, in which case their illness is considered treatment-resistant.2,3

As explained by Prof Correll, the problem of lacking or inadequate response to treatment reaches beyond the acute illness phase because repeated relapse - possibly reflecting periods of disease progression - increases the risk of non-response to subsequent antipsychotic treatment.4 Therefore, preventing relapse by early and effective pharmacological intervention is critical not only for treating acute symptoms; it may also change the course of disease and improve prognosis, including long-term functional outcomes.5

Early and effective pharmacological intervention has the potential to change the prognosis of schizophrenia, but persistent symptoms and treatment-resistance are common problems

But what can be done in clinical practice to optimize treatment outcomes and thereby counter partial response, relapse and the development of treatment-resistance? According to the Professor, the focus should be on optimization of the current treatment via dose increase rather than augmentation with other - antipsychotic or non-antipsychotic – medication, which is less supported by evidence.6 Pointing out treatment non-adherence as the single most important risk factor for relapse, he emphasized the critical importance of ensuring patient adherence to treatment, with the use of long-acting injectable formulations as an important means to overcoming the adherence challenges in maintenance treatment associated with oral antipsychotic treatment.7


Looking beyond positive symptoms to improve treatment outcomes

Highlighting the heterogeneity of schizophrenia, Professor Correll then widened the scope to the range of clinical domains that are affected in schizophrenia, which - in addition to positive symptoms - includes negative symptoms, cognitive dysfunction, affective symptoms and motor symptoms.

Positive symptoms are generally reduced and stabilized over time with antipsychotic treatment, but negative symptoms and cognitive impairment tend to show less improvement with antipsychotic treatment and persist during remission from positive symptoms.

Focusing on negative symptoms and cognitive impairment, Prof Correll emphasized that these symptom domains - despite their enormous negative impact on clinical outcomes, patient functioning and quality of life8,9 - tend to be less in focus as treatment targets. Presenting cross-sectional data indicating that the cognitive impairments in first-episode patients are comparable to those seen in patients with chronic schizophrenia,10 the Professor explained that whereas positive symptoms are generally reduced and stabilized over time with antipsychotic treatment, negative symptoms and cognitive impairment precede the onset of diagnostic positive symptoms, show less improvement with antipsychotic treatment, and tend to persist even during remission from positive symptoms.11

Prof Correll urged an increased focus on the prevalence and burden of negative and cognitive symptoms, and that all relevant clinical domains be considered and addressed at an early stage to improve treatment outcomes. He concluded his talk by emphasizing the need for new treatments for patients with persistent symptoms in each of these domains.


Educational financial support for this satellite symposium was provided by H. Lundbeck A/S

Our correspondent’s highlights from the symposium are meant as a fair representation of the scientific content presented. The views and opinions expressed on this page do not necessarily reflect those of Lundbeck.


1. Leucht et al. Am J Psychiatry 2017; 174 (10): 927–942.

2. Lally et al. Psychol Med 2016;46(15):3231–3240;

3. Lieberman. J Clin Psychiatry 1999;60(Suppl. 12):9–12;

4. Takeuchi et al. Neuropsychopharmacology 2019; 44 (6): 1036–1042.

5. Schooler et al. J Clin Psychiatry 2016; 77 (5): 628–634.

6. Correll et al. JAMA Psychiatry 2017; 74 (7): 675–684.

7. Kishimoto et al. Schizophr Bull 2018; 44 (3): 603–619.

8. Correll. J Clin Psychiatry 2013; 74 (2): e04.

9. Bowie et al. Biol Psychiatry 2008; 63 (5): 505–511.

10. Sponheim et al. J Psychiatr Res 2010; 44 (7): 421–428.

11. Austin et al. Schizophr Res 2015; 168 (1–2): 84–91.