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A Multi-Target Drug Treatment in Schizophrenia and Schizoaffective Disorder Using Adjunctive Agents with Non-D2 Mechanisms of Action

Abstract

Pharmacologic actions to reduce neurotransmission through the D2 receptor have been the only proven therapeutic mechanism for schizophrenia (SZ) and schizoaffective (SA) disorder. However, in view of the multifactorial genesis and pathogenesis of these psychoses, it is unlikely that any antipsychotic drug would work equally well against all symptoms and behavioral disturbances. The absence of a single therapeutic target for SZ/SA disorder has prompted the use of polypharmacy strategies including multi-target pharmacotherapy, consisting of various add-on medications and supplements. Multi-target polypharmacy strategies include the off-label prescription of adjunctive agents such as antidepressants, mood stabilizers, and benzodiazepines already in use, and novel potential adjunctive agents (newer molecules or compounds) based on several non-dopaminergic hypotheses (serotonergic, noradrenergic, glutamatergic, gamma-aminobutyric acid related, and cholinergic neurotransmission, neuroprotective mechanisms and brain neuroplasticity). This chapter is an overview of the current state of evidence for the augmentation of antipsychotics with antidepressants, lithium, antiepileptic agents, benzodiazepines, and new molecules and compounds for the treatment of people with SZ/SA disorder with a special focus on research data published within the past 5–7 years. Using these agents for the augmentation of antipsychotics based on a multi-target drug treatment approach entails the combination of two or more drugs/agents with different mechanisms of action on the central nervous system in an attempt to enhance efficacy.

Keywords

  • Augmentation
  • Antidepressants
  • Mood stabilizers
  • Lithium
  • Antiepileptic drugs
  • Benzodiazepines
  • Schizophrenia
  • Schizoaffective disorder
  • Hormones
  • Supplements

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Fig. 8.1
Fig. 8.2
Table 8.1

Abbreviations

AMPA:

dl-α-NH2-2,3-dihydro-5-methyl-3-oxo-4-isoxazolepropanoic acid

BDNF:

Brain-derived neurotrophic factor

BZD:

Benzodiazepines

CATIE:

Clinical Antipsychotic Trials of Intervention Effectiveness

CNS:

Central nervous system

COX:

Cyclo-oxygenase

DA:

Dopamine

DHEA:

Dehydroepiandrosterone

DHEA(S):

Both DHEA and DHEAS

DHEAS:

Dehydroepiandrosterone sulfate

EPA:

Eicosapentaenoic acid

FGAs:

First generation antipsychotics

GABA:

γ-amino-butyric acid

GSK:

Glycogen synthase kinase

HPA:

Hypothalamic-pituitary-adrenal axis

NMDA:

N-methyl-d-aspartate

PANSS:

Positive and Negative Symptom Scale

PREG:

Pregnenolone

PREG(S):

Both PREG and PREGS

PREG(S)/DHEA(S):

Both PREG(S) and DHEA(S)

PREGS:

Pregnenolone sulfate

SAMe:

S-adenosyl L-methionine

SANS:

Scale for the Assessment of Negative Symptoms

SGAs:

Second generation antipsychotics

SSRI:

Selective serotonin re-uptake inhibitor

SZ/SA:

Schizophrenia and schizoaffective disorder

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Acknowledgements

I wish to express gratitude to Ms. Rena Kurs, B.A. (Shaar-Menashe Mental Health Center, Hadera, Israel) for editorial assistance.

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Ritsner, M.S. (2013). A Multi-Target Drug Treatment in Schizophrenia and Schizoaffective Disorder Using Adjunctive Agents with Non-D2 Mechanisms of Action. In: Ritsner, M. (eds) Polypharmacy in Psychiatry Practice, Volume I. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-5805-6_8

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