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2. Management of Negative Symptoms
David N. Osser, MD
Associate Professor of Psychiatry
Harvard Medical School
Brockton Division of the VA Boston Healthcare System
General Editor - Psychopharmacology Algorithm Project
Harvard South Shore Residency Training Program

3. Negative symptoms Decreased motivation Decreased affective intensity
Decreased emotional range
Paucity of communication

4. Negative symptoms Decreased motivation Decreased affective intensity
Decreased emotional range
Paucity of communication
Primary
Secondary

5. Negative symptoms Decreased motivation Decreased affective intensity
Decreased emotional range
Paucity of communication
Primary
Secondary
Positive symptoms
Depression
Medication side effects
EPS
Dystonia
Sedation

6. Negative symptoms Decreased motivation Decreased affective intensity
Decreased emotional range
Paucity of communication
Primary
Secondary
Positive symptoms
Depression
Medication side effects
EPS
Dystonia
Sedation

7. Negative symptoms Decreased motivation Decreased affective intensity
Decreased emotional range
Paucity of communication
Primary
Secondary
Positive symptoms
Depression
Medication side effects
EPS
Dystonia
Sedation

8. Negative symptoms Decreased motivation Decreased affective intensity
Decreased emotional range
Paucity of communication
Primary
Secondary
Positive symptoms
Depression
Medication side effects
EPS
Dystonia
Sedation
Treat

9. Negative symptoms Decreased motivation Decreased affective intensity
Decreased emotional range
Paucity of communication
Primary
Secondary
Positive symptoms
Depression
Medication side effects
EPS
Dystonia
Sedation
Treat
Manage

10. Primary negative symptoms

11. Negative symptoms Decreased motivation Decreased affective intensity
Decreased emotional range
Paucity of communication
Primary
Secondary
Poorly responsive to all antipsychotics

12. Efficacy for clozapine
Positive symptoms
Efficacy for clozapine
Clozapine
Negative symptoms
No efficacy
Buchanan, R. W., Breier, A., Kirkpatrick, B., Ball, P., & Carpenter Jr, W. T. (1998). Positive and negative symptom response to clozapine in schizophrenic patients with and without the deficit syndrome. American Journal of Psychiatry, 155(6),

13. Antidepressants Antipsychotics Fluoxetine Mirtazapine FGA Risperidone
Trazodone
Singh, S. P., et al (2010). Efficacy of antidepressants in treating the negative symptoms of chronic schizophrenia: meta-analysis. The British journal of psychiatry, 197(3),
Rado, J. T. (2011). Treatment of negative symptoms in schizophrenia. Psychopharm Review, 46(5),
Silver, H., et al (2013). Add-on fluvoxamine and negative symptoms of schizophrenia: analysis of data from augmentation studies in a single center. Journal of clinical psychopharmacology, 33(5),

14. Antidepressants Antipsychotics EPS component? Fluoxetine Mirtazapine
FGA
Risperidone
Trazodone
EPS component?
Singh, S. P., et al (2010). Efficacy of antidepressants in treating the negative symptoms of chronic schizophrenia: meta-analysis. The British journal of psychiatry, 197(3),
Rado, J. T. (2011). Treatment of negative symptoms in schizophrenia. Psychopharm Review, 46(5),
Silver, H., et al (2013). Add-on fluvoxamine and negative symptoms of schizophrenia: analysis of data from augmentation studies in a single center. Journal of clinical psychopharmacology, 33(5),

15. Fluvoxamine If adding an antidepressant:
Caution about pharmacokinetic and pharmacodynamic interactions
If adding an antidepressant:
Fluvoxamine
CYP450 1A2 inhibitor
Can increase clozapine levels up to 500%
Reduce clozapine dose

16. Fluvoxamine Citalopram If adding an antidepressant:
Caution about pharmacokinetic and pharmacodynamic interactions
If adding an antidepressant:
Citalopram
Increases clozapine levels (unknown mechanism)
QTc prolongation
Fluvoxamine
CYP450 1A2 inhibitor
Can increase clozapine levels up to 500%
Reduce clozapine dose

17. Fluvoxamine Citalopram If adding an antidepressant:
Caution about pharmacokinetic and pharmacodynamic interactions
If adding an antidepressant:
Citalopram
Increases clozapine levels (unknown mechanism)
QTc prolongation
Fluvoxamine
CYP450 1A2 inhibitor
Can increase clozapine levels up to 500%
Reduce clozapine dose

18. Fluvoxamine Citalopram If adding an antidepressant:
Caution about pharmacokinetic and pharmacodynamic interactions
If adding an antidepressant:
Citalopram
Increases clozapine levels (unknown mechanism)
QTc prolongation
Fluvoxamine
CYP450 1A2 inhibitor
Can increase clozapine levels up to 500%
Reduce clozapine dose

19. Fluvoxamine Citalopram If adding an antidepressant:
Caution about pharmacokinetic and pharmacodynamic interactions
If adding an antidepressant:
Citalopram
Increases clozapine levels (unknown mechanism)
QTc prolongation
Fluvoxamine
CYP450 1A2 inhibitor
Can increase clozapine levels up to 500%
Reduce clozapine dose

20. Experimental treatments
Memantine
D-serine
Sarcosine
Selegiline
Ginkgo biloba
Minocycline
Rezaei, F., et al (2013). Memantine add-on to risperidone for treatment of negative symptoms in patients with stable schizophrenia: randomized, double-blind, placebo-controlled study. Journal of clinical psychopharmacology, 33(3),
Levkovitz, Y., et al (2010). A double-blind, randomized study of minocycline for the treatment of negative and cognitive symptoms in early-phase schizophrenia. Journal of Clinical Psychiatry, 71(2), 138.
Doruk, A., Uzun, Ö., & Özsahin, A. (2008). A placebo-controlled study of extract of ginkgo biloba added to clozapine in patients with treatment-resistant schizophrenia. International clinical psychopharmacology, 23(4),

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