Pharmacological treatment of negative symptoms in schizophrenia: update and proposal of a clinical algorithm

Figures & data

Table 1 Subscales in the Brief Negative Symptom Scale

Subscale	Item	AAA factor	EXP factor
Anhedonia	Intensity of pleasure Frequency of pleasurable activities Intensity of expected pleasure	✓ ✓ ✓
Lack of normal distress	Lack of normal distress^a
Asociality	Asociality: behavior Asociality: internal experience	✓ ✓
Avolition	Avolition: behavior Avolition: internal experience	✓ ✓
Blunted affect	Facial expression Vocal expression Expressive gestures		✓ ✓ ✓
Alogia	Quantity of speech Spontaneous elaboration		✓ ✓

Notes: Data from Kirkpatrick et al.^{28 a}Lack of normal distress usually does not load strongly onto either factor.

Abbreviations: AAA, anhedonia/asociality/avolition; EXP, expressivity.

Table 2 Summary of the main characteristics of medications on schizophrenia NS

Drug class		Main characteristics in NS
Antipsychotics	FGA	May affect patients’ functional outcomes by inducing neuromotor disorders, worsening NS, social withdrawal, and cognitive dysfunction
SGA	More efficacious (amisulpride, clozapine, olanzapine, and risperidone) than or as efficacious (aripiprazole, quetiapine, sertindol, ziprasidone, and zotepine) as FGA in the treatment of PS and NS, with often larger effect size on NS than PS Associated with lower cognitive impairment and better functional outcomes Amisulpride Effective on predominant NS Combined antidepressant effect that may act on secondary NS Cariprazine More effective than risperidone in reducing specifically NS (no effect on depression and PS) Superior results compared with risperidone in real-world outcomes (personal and social performance and quality-adjusted life-years) Olanzapine More effective than haloperidol in reducing NS Quetiapine More effective than risperidone in reducing NS, but not PS
Antidepressants (add-on)		May improve NS and some affective disorders associated with schizophrenia The mechanism of action is still to be clarified Fluoxetine, paroxetine, seligiline, citalopram, reboxetine, fluvoxamine, and mirtazapine Effective in reducing NS in patients with predominant NS Lower effect size on depressive symptoms, possible independent action on NS Amitriptyline, mianserin hydrochloride, trazodone hydrochloride, paroxetine, fluoxetine, or fluvoxamine Medium to high effect size in reducing core NS in patients with mainly NS

Abbreviations: FGA, first-generation antipsychotic; SGA, second-generation antipsychotic; NS, negative symptoms; PS, positive symptoms.

Figure 1 Clinical management of negative symptoms in schizophrenia.

Abbreviations: PNS, predominant negative symptoms; FGA, first-generation antipsychotic; SGA, second-generation antipsychotic.