7 X 11.5 Three Lines.P65

Cambridge University Press 978-0-521-71413-6 - Antipsychotics and Mood Stabilizers: Stahl’s Essential Psychopharmacology, Third Edition Stephen M. Stahl Index More information

Index

Page numbers followed by ‘f ’ indicate ﬁgures; page numbers followed by ‘t ’ indicate tables.

3PPP, 134f agitation, benzodiazepines for, 188 AAADC (aromatic amino acid decarboxylase), and receptor conformation, 132f 97, 98f agranulocytosis, clozapine and, 164 ABT089, 203 akathisia acetylcholine (ACh), from aripiprazole, 175 in arousal pathways, 150, 152f nigrostriatal pathway dopamine deﬁciencies and blocked dopamine receptors, 93f and, 31 overactivity, 95 alanine-serine-cysteine transporter (ASC-T), reciprocal relationship with dopamine, 92f glial, 34 acetylcholine-linked mechanisms, 202 alogia, 5, 6t ACP 103, 200 alpha 1 adrenergic receptors ACP-104, 129, 134f atypical antipsychotic agents and, 139f ACR16, 134f and sedation, 151f adipose tissue, insulin resistance in, 141, alpha-1 receptor, antagonism, 94f 144f alpha-2 adrenergic receptors, atypical adolescence antipsychotic agents and, 139f aggressiveness in, 179 alpha 2 antagonists, 168 removal of synaptic connections, 68 alpha-4 beta-2 nicotinic acetylcholine receptor, risperidone for treating psychotic disorders, 203 166 alpha-7-nicotinic cholinergic agonists, affective blunting, 5 202 affective ﬂattening, as SSRI side effect, 110 alpha amino-3-hydroxy-5-methyl-4- affective symptoms isoxazolepropionic acid (AMPA) dorsal vs. ventral regulation, 76f receptors, 40, 40f, 66f mesolimbic dopamine pathway role in, 28 synapses with, 67f multiple disorders impacting, 15f Alzheimer’s disease, 180 pharmacy, 182, 184f cognitive symptoms, 13 in schizophrenia, shared with other disorders, excitotoxicity and, 56, 57f 14 symptoms shared with schizophrenia, 12, 13, aggressive symptom pharmacy, 181f 13f aggressiveness, 10 amantadine, 194 multiple disorders impacting, 15f, 16f amenorrhea, 32, 90 in schizophrenic patients, 13 d-amino acid oxidase (DAO), 38f, 39

219

© Cambridge University Press www.cambridge.org Cambridge University Press 978-0-521-71413-6 - Antipsychotics and Mood Stabilizers: Stahl’s Essential Psychopharmacology, Third Edition Stephen M. Stahl Index More information

amisulpride, 130, 134f, 135f, 176, 183 and prolactin, 118f and cardiometabolic risk, 140t risk and benefits of long-term, 95 clinical actions of, 125 in use, 85t and diabetes, 171 as D2 dopamine receptor blockers, 27 for negative symptoms in schizophrenia, 182f first-generation, 83f, 96 pharmacological icon, 177f high doses, 191f and QTc prolongation, 171 links between binding properties and clinical amoxapine (Asendin), 173, 174f actions, 136 AMPA (alpha-amino-3-hydroxy-5-methyl-4- low-potency, and dissociation, 124 isoxazole-priopionic acid) glutamate “off-label” uses, 82 receptors, 64 patient toleration of, 163 and synaptogenesis, 62 pharmacokinetics, 156–162 AMPA-kines, 199 pharmacological properties, 162–179 amphetamines, 44 prescribing information, 82 and dopamine release, 26 prophylactic, 192 response to emotional input, 78 receptor interactions for, 134 and schizophrenia symptoms, 75, 77f sedation as short-term tool, 152f amylin, 204 side effects and compliance, 153f anhedonia, 5, 6t, 30 switching, 185, 187f antagonists, process to avoid, 187f vs. inverse agonist, 105 from sedating to nonsedating, 189f vs. partial agonists, 132f antisocial personality disorder, 13 presynaptic, 199f anxiety disorders anticholinergic agents 5HT1A receptors and, 103f D2 antagonism and, 93f quetiapine for, 168f side effects, 95 anxious mood, 14 antihistamines, 82 anxious self-punishment, 3 atypical, 96 apathy, 3 administration frequency, 122 histamine-1 with 5HT2C antagonism, 141f cardiometabolic risk and, 140t aripiprazole, 129, 130, 134f–136f, 158, 175, 183 cardiometabolic risk management, 145 and cardiometabolic risk, 140t hit-and-run receptor binding properties, as CYP 2D6 substrate, 158, 159f 124f and diabetes, 171 hypothetical action over time, 125f dosage with carbamazepine, 161f, 162 to improve schizophrenia symptoms, 109 pharmacological icon, 176f pharmacological properties, 139f raising levels of, 160f and prolactin, 118f and sedation, 184, 186f properties, 119, 135f switching from sedating agent to, 189 and weight gain risk, 140t and weight gain risk, 140t avoiding sedation and enhancing long-term aromatic amino acid decarboxylase (AAADC), outcome, 155f 97, 98f benzodiazepines to lead in or top off, 188f asenapine, 122f, 200 best practices for monitoring and managing, Asendin (amoxapine), 173, 174f 149f asociality, 5, 6t cardiometabolic risk and, 137–150 assaultiveness, 10 combining two, 191 atorvastatin conventional, 91f impaired, in schizophrenia, 11 vs. atypical, 112f, 114f attention deficit hyperactivity disorder D2 binding of, 123f (ADHD), 180 D2-receptor antagonist, 83 symptoms shared with schizophrenia, 14 hypothetical action over time, 123f attitudes, hostile, 3 muscarinic cholinergic blocking properties, atypical antipsychotic agents, 96 91, 95 administration frequency, 122 pharmacological properties, 82–96 cardiometabolic risk and, 140t

220 Index

cardiometabolic risk management, 145 brain. See also circuits clozapine as, 163 dopamine pathways in, 26f, 22–29 vs. conventional, 112f, 114f excitotoxicity in early development, 62f hit-and-run receptor binding properties, 124f insult and schizophrenia, 57 hypothetical action over time, 125f survival of wrong neurons, 59 properties, 119, 139f focus on malfunctioning areas, 16 and weight gain risk, 140t glutamate pathways in, 43f, 41–45 auditory hallucinations, 5 nucleus accumbens as pleasure center, 83 autism, 180 brain circuits, and schizophrenia symptoms, 14 cognitive symptoms, 13 brain damage, 180 irritability in children with, 181 brain-derived neurotrophic factor (BDNF), 58 risperidone for irritability, 166 5HT6 receptors and, 201 avolution, 5, 6t genes coding for, 63f “awakening”, 164, 191 and long-term memory formation, 99 and synapse formation, 62, 65f benzamide antipsychotics, clinical actions of, Brief Psychiatric Rating Scale, 7t 125 burnout benzodiazepines, 153, 155f, 180 of neuronal systems, 28 for aggression management, 181f in schizophrenic patients, 54, 55f for agitation, 188 buspirone, 201 injectable, 179 to lead in or top off antipsychotics, 188f calcium when switching antipsychotics, excessive 189f and excitotoxicity, 58f bifeprunox (DU 127090), 129, 130, 134f–136f, overexcitation and dangerous opening of, 55 177 calcyon, genes for, 73f and cardiometabolic risk, 140t cannabinoid antagonists, 203 and diabetes, 171 carbamazepine (Equetro), 160 in metabolic pharmacy, 183 CYP450 3A4 and discontinuation, 162f metabolized by CYP 3A4, 158 CYP450 3A4 induced by, 161f for obesity, 202 antipsychotic agents and, 143f, 171 pharmacological icon, 178f atypical antipsychotic agents and, 139, 140t and sedation, 186f clozapine and, 164 sedation risk with, 184 low risk antipscychotic agents, 140t bipolar disorder. See also mood stabilizers olanzapine and, 165 bifeprunox for treating, 178 receptors mediating, 139f depressed phase of, 169 cardiovascular disease olanzapine and, 165 atypical antipsychotic agents and, 137 risperidone effectiveness for, 167 risk of, 142f symptoms shared with schizophrenia, 12, 13, cardiovascular side effects, of antipsychotic 13f drugs, 95 ziprasidone for, 170 catabolic enzymes, blame, 3 and dopamine breakdown, 21, 21f blonanserin, 122f and dorsolateral prefrontal cortex, 19f blood pressure genes for, 73f monitoring, 146, 150f CATIE (Clinical Antipsychotic Trials of blunted affect, 6t Intervention Effectiveness), 153f blurred vision, from conventional cerebral cortex, antipsychotics, 92f antipsychotic agent binding to postsynaptic BMY-14802, 200 5HT2A receptors, 114f body mass index (BMI), 142f aggressiveness in, 179 baseline measurement, 149f psychotic illness, symptoms shared with monitoring, 150f schizophrenia, 12, 13, 13f borderline personality disorder, 13, 180 risperidone for, 166

Index 221

chlorpromazine (Thorazine), 82, 85t in schizophrenia, shared with other disorders, cholecystokinin (CCK), 204 13, 14f chorea, dopamine hyperactivity in nigrostriatal serotonin receptors and, 99 pathway and, 31 cognitive symptom pharmacy, 182, 183f CHRNA (alpha-7 nicotinic cholinergic “combos” (combination of medications) receptor), 72f for schizophrenia, 190, 204 circadian rhythms for symptom reduction in psychosis, 179 5HT7 receptors and, 103f communication Cl1007, 134f dysfunction of, 5 Clinical Antipsychotic Trials of Intervention inhibitors, 202 Effectiveness (CATIE), 153f conceptual disorganization, 3 clinical practice conduct disorder, 179 vs. clinical trials, 178 connectivity, genes affecting, 58 symptom treatment, vs. disease treatment, constipation 179 from conventional antipsychotics, 92f Clopixol (zuclopenthixol), 85t and emotion and cognitive symptoms, clozapine, 136f, 157, 157f, 158, 184 17f 5HT6-antagonist properties of, 201 and schizophrenia symptoms, 15 for affective symptoms in schizophrenia, cortical arousal, neurotransmitters of, 152f 183 cortical brainstem glutamate projection, 43f, for aggression management, 180, 181f 44f and antagonism of muscarinic cholinergic cortical pyramidal neurons receptor, 146f inhibition by 5HT1A receptors, 103f augmenting, 191 cortico-striatal-thalamic-cortical (CSTC) binding properties, 163f loops, 46, 47f and cardiometabolic risk, 140t corticoaccumbens projections, NMDA as CYP 2D6 substrate, 158, 159f glutamate receptor hypofunction in, 51f dosage with carbamazepine, 161f, 162 corticobrainstem glutamate pathways M3 receptors blocked by, 146f neurons, 45 for negative symptoms in schizophrenia, and NMDA receptor hypofunction 182f hypothesis of schizophrenia, 42–45 pharmacological icon, 163f corticocortical glutamate pathways, 43f, 48–52 pharmacological properties, 163 NMDA receptor regulation of, 53f potency, and dissociation, 124 corticostriatal glutamate pathways, 43f, 46 raising levels of, 160f corticothalamic glutamate pathways, 43f, 46 rebound psychosis from discontinued, 185 cross titration, 186, 187f for sedation, 185 getting caught in, 188f for suicide reduction, 164, 184f CX516, 199 for symptom reduction in psychosis, 179 CX546, 200 and weight gain risk, 140t CX619/Org 24448, 200 cocaine, cyamemazine (Tercian), 85t, 96, 175 and dopamine release, 26 pharmacological icon, 175f as antipsychotic side effect, 95 cyclic AMP (adenosine monophosphate), from conventional antipsychotics, 92f disruptions in, 70f as SSRI side effect, 110 d-cycloserine, 195, 197, 197f cognitive functioning, cytochrome P450 (CYP450) enzyme systems, 5HT1A receptors and, 103f 156, 156f 5HT2C receptors and, 103f CYP450 1A2 substrates, 157, 157f dorsolateral prefontal cortex (DLPFC) and, and smoking, 158, 158f 18f, 27 CYP450 2C9, 158 impaired, 153 CYP450 2C19, 157 sedation and somnolence and, 154 CYP450 2D6, 157, 158, 159f mesocortical prefrontal cortex and, 17f antidepressants as inhibitors, 160f quantifying, 11 genetic polymorphism for, 157, 157f

222 Index

in risperidone conversion to paliperidone, DMXB-A {3-[(2, 4-dimethoxy) benzylidene] 159f, 160f anabaseine}, 203 inhibitors, 161f Dolmatil (sulpiride), 85t, 96, 129, 130, 134f, CYP450 3A4, 158 135f, 177 inducers, 160 clinical actions of, 125 types, 156 pharmacological icon, 177f dopa decarboxylase (DDC), 20, 20f d-amino acid oxidase activator (DAOA), 69f dopamine, 18, 72f and NMDA receptor regulation, 68, 68f 5HT2A antagonists stimulation of release, d-amino acid oxidase (DAO), 68, 69f 105 DDC (DOPA decarboxylase), 20, 20f and acetylcholine activity, 93f death. See also neurons, cell death acetylcholine release inhibition, 94 premature agonist actions at 5HT1A receptors and, 131 atypical antipsychotic agents and, 137 in arousal pathways, 150 risk of, 142f brain pathways, 26f, 22–29 delusions, 2, 4 deficit in mesocortical projections to antipsychotic action to reduce, 179 dorsolateral prefrontal cortex, 28 mesolimbic dopamine pathway role in, 26 diverse levels in brain subsections, 29 reduction with mesolimbic D2 receptor dorsolateral prefontal cortex regulation by, block, 90 19f dementia. See also Alzheimer’s disease genes influencing, 19f behavioral disturbances, 181 hit-and-run theory, 127f poststroke, cognitive symptoms, 13 interaction with serotonin, in nigrostriatal psychosis with, 166 dopamine pathway, 107f, 111f symptoms shared with schizophrenia, 12, 13f levels in untreated schizophrenia, 127f excitotoxicity for pruning, 56 neuronal tuning, 29 Depixol (flupenthixol), 85t neurotransmission spectrum, 128f depressed mood, 14 untreated schizophrenia and after 5HT1A receptors and, 103f serotonin dopamine antagonist, 120f depressive psychosis, 3 pharmacologic mechanisms influencing, 19f diabetes mellitus, prolactin inhibition by, 117f atypical antipsychotic agents and, 137 reciprocal relationship with acetylcholine, 92f zotepine and, 172 5HT1A and 5HT2A receptor regulation, diabetic ketoacidosis (DKA), 143, 147f, 149f 99, 100 clozapine and, 164 5HT2C receptors and, 103f olanzapine and, 165 serotonin inhibition of, 106f risperidone and, 167 serotonin receptors influence on, 105f 3-[(2, 4-dimethoxy) benzylidene] anabaseine serotonin regulation of, 108f –110f (DMXB-A), 203 synthesis, 20f DISC-1 (disrupted in schizophrenia-1), 59, 61, termination of action, 21f 64f and thalamic filter, 48f genes for, 63f, 70f tuning output with serotonin 2A/dopamine-2 and glutamate synapses strengthening, 62, 66f antagonists, 119 and NMDA receptor regulation, 68f dopamine D1-selective agonists, 202 and NMDA regulation, 71 dopamine D2 partial agonists, 96, 128f, 129, and synapse formation, 62, 65f 129f and synaptic vesicle transport, 71 aripiprazole as, 175 disinhibition, 100 dopamine D2 receptor agonists, 128f, 129 disorganized/excited psychosis, 3 dopamine D2 receptors, 21 disorientation, 3 antagonists, 83, 83f, 84f, 91, 96, 129 divalproex (Depakote), and anticholinergic agents, 93f for schizophrenia, 190 integrated theory of schizophrenia and, 88f adding to antipsychotic, 191f mesocortical dopamine pathway and, 85f divine mission, 3 nigrostriatal dopamine pathway and, 86f

Index 223

dopamine D2 receptors, (Contd.) drug interactions, 162 rapid dissociation of 122f dry mouth tuberoinfundibular dopamine pathway and, from conventional antipsychotics, 92f 88f dysbindin, 59 blockade in nucleus accumbens, 107 genes coding for, 63f continuous occupancy, 169 and glutamate synapses strengthening, 62, conventional antipsychotic binding to, 119 66f dilemma of blocking in all dopamine and NMDA receptor regulation, 68f pathways, 90 and NMDA regulation, 71 output, 129f and synapse formation, 62, 65f presynaptic, 21, 23f, 24f vGluT regulated by, 71 rapid dissociation from, 119, 121 dysconnectivity, 59 side effects of unwanted blockade, 136 dyskinesias, dopamine hyperactivity in somatodendritic, 25f nigrostriatal pathway and, 31, 32f dopamine D3 antagonists, 202 dyslipidemia, 139 “dopamine hypothesis of schizophrenia”, 27 aripiprazole and, 176 dopamine neurons, 105 atypical antipsychotic agents and, 137 dopamine partial agonists (DPAs), 125, 127f, blood pressure monitoring, 146 180f ziprasidone and, 171 for aggression management, 181f zotepine and, 172 for cognitive function improvement, 182f dystonia, nigrostriatal pathway dopamine in development, 134f deficiencies and, 31 development of new, 202 dystrobrevin-binding protein 1, 58 for first-line treatment of schizophrenia positive symptoms, 179 efficacy, path to, 155f integrated theory of schizophrenia and, 132f efficacy profile, 154f on market, 134f elderly in mesolimbic pathway, 130f risperidone for, 166 for negative symptoms in schizophrenia, 182f EMD128130 (sarizotan), 134f, 202 and nigrostriatal pathway, 131f emotion spectrum, 135f amygdala response to input, 78 switching from SDA to, 190f brain component regulating, 16 dopamine receptors, 21, 22f mesocortical prefrontal cortex and, 17f dopamine transporter (DAT), 20, 21f, 22f mesolimbic dopamine pathway role in, 28 and dorsolateral prefrontal cortex, 19f brain areas impacting, 75 dopaminergic neurons, 20–22 eplivanserin (SR 46349), 201 cognition regulation by, 27 ERB signaling system, neuregulin activation of, cognitive symptoms and, 18f 71 dopamine deficit in mesocortical projections essential amino acids, 39 to, 28 Essential Psychopharmacology: The Prescriber’s genes influencing, 19f Guide (Stahl), 162, 163 information processing involving, 73 excitatory amino acid transporters (EAAT), 33, mesocortical dopamine pathway, 29f 40f mesolimbic dopamine pathwaysin for glutamate takeup, 35f schizophrenia, 85f “excitotoxic hypothesis of schizophrenia”, 54 regulation by dopamine and serotonin, 19f excitotoxicity, 57f and schizophrenia symptoms, 15, 76f cellular events during, 58f –61f from histamine-1 receptor blockade, 95 in early fetal brain development, 62f drug abuse, 179 and glutamate systems, 55, 194 by schizophrenic patients, 90 and neuronal insult, 57 symptoms shared with schizophrenia, 13 executive dysfunction, 11 drug-induced parkinsonism, 86 impaired drug-induced psychoses, symptoms shared with in schizophrenia, 11 schizophrenia, 12 by mesocortical dopamine pathway, 27

224 Index

extrapyramidal symptoms (EPS), 121, 123f glucose 5HT2A antagonist to reduce, 105, 107 monitoring fasting, 146 absence with atypical antipsychotics, 125f agonist actions at 5HT1A receptors and, D2 receptor blockage and, 86 131 dopamine partial agonism and, 132f conversion to glutamine, 34, 35f risperidone and, 166 system overactivity, 28, 55 from unwanted D2 receptor blockade, 136 key pathways in brain, 43f, 41–45 NMDA hypofunction hypothesis of fasting triglycerides schizophrenia and, 42–45 antipsychotic agents and, 145f NMDA receptor excitation spectrum by, baseline measurement, 145, 149f 57f monitoring, 150f pharmacology, 194 quetiapine and, 169 preventing release, 199f rapid elevation of, 141 recycled and regnerated, 35f risperidone and, 167 conversion to glutamine, 36f ziprasidone and, 171 glutamine release from glial cells, 36f fear. See also anxiety disorders 5HT1A and 5HT2A receptor effect, processing by amygdala, 77f 115f excitotoxicity in early development, 62f regulation with 5HT1A, 113, 116 insult and schizophrenia, 57 role in schizophrenia pathophysiology, 33 survival of wrong neurons, 59 susceptibility gene effect on, 71 insults in neurodegenerative theories of synapses, convergence of susceptibility genes schizophrenia, 54f for schizophrenia on, 68 first-generation antipsychotic agents, 83f, 96 synthesis, 33 fluoxetine (Prozac), glutamate receptors, 39, 40f metabolite of, 159 metabotropic, 39, 42f olanzapine and, 165 types, 41t flupenthixol (Depixol), 85t glutamatergic corticostriatal projections, fluphenazine (Prolixin), 85t NMDA glutamate receptor fluvoxamine, 159, 200 hypofunction in, 51f free radicals, 60f glutaminase, 34, 36f and neuron death, 56 glutamine scavengers for excitotoxicity, 196f glutamate conversion to, 34, 35f release from glial cells, 36f G protein-linked receptors, 103f glutamine synthetase, 34 GABA (gamma-aminobutyric acid), 44f, 72f glycine, 197, 197f GABA (gamma-aminobutyric acid) neurons, from glial cells, 38 46, 47f from l-serine, 39 for connecting serotonin and dopamine production, 37 neurons, 105 glycine agonists, 195 dopamine impact on, 48f glycine transporters (GlyT1), 196 release, 105f inhibitors, 198f galactorrhea, 32, 90 grandiose expansiveness, 3 genes guilt, 14 susceptibility, 58 CYP450 enzymes in wall, 156 for schizophrenia, 63t, 73 GW742457, 201 genetic programming, in neurodegenerative theories of schizophrenia, 54f H1 histamine receptor, and weight gain, 137 glial alanine-serine-cysteine transporter hallucinations, 2, 5 (ASC-T), 34 5HT2A receptors and, 103f glutamine release from, 36f 5HT2A receptors effect on glutamate release glycine from, 38 and, 113 glial d-serine transporter, 38f antipsychotic action to reduce, 179 glial SNAT, 34, 36f, 38 mesolimbic dopamine pathway role in, 26

Index 225

hallucinations (Contd.) ion channel-linked receptors, 40 reduction with mesolimbic D2 receptor ionotrophic receptors, 40 block, 90 irritability, 14 serotonin receptors and, 99 voices in, 2 judgment, distortions in schizophrenia, 78 haloperidol (Haldol), 85t, 91f, 95 histamine, kainite receptors, 40, 40f in arousal pathways, 150, 152f and schizophrenia symptoms, 43, 194 antagonism, 94f ketoconazole, 159 atypical antipsychotic agents and, 139f blockade of, 95 lactation, 32 and sedation, 151f for schizophrenia, 190 histamine-1, with serotonin-2C antagonist, and adding to antipsychotic, 191f appetite stimulation, 141f language, odd use of, 11 ”hit and run” binding, 121 lazaroids, as free radical scavenger, 196f hostile belligerence, 3 life expectancy, of schizophrenic patients, 4 hydroxy-pyruvate (OH-pyruvate), 38f, 39, 69f ligand-gated ion channels, 40f 9-hydroxy-risperidone, 167. See also lithium, 190 paliperidone for affective symptoms in schizophrenia, 183 5-hydroxytryptophan (5HTP), 97, 98f for suicide reduction, 183, 184f of mesolimbic dopamine pathway, 27 liver hyperglycemic hyperosmolar syndrome (HHS), CYP450 enzymes in, 156 143, 147f, 149f insulin resistance in, 141, 144f clozapine and, 164 long-term potentiation (LTP), 62, 66f olanzapine and, 165 low-potency antipsychotic agents, and risperidone and, 167 dissociation, 124 hyperinsulinemia, 137 loxapine (Loxitane), 85t, 96 hyperprolactinemia, 90 5HT6-antagonist properties of, 201 5HT2A antagonists and reduction of, 116 pharmacological icon, 174f from unwanted D2 receptor blockade, 136 luxapine, 173 hypothalamic nuclei, LY 293558, 200 dopamine pathway from, 26f, 33 “master switch”, 41 iloperidone, 122f, 200 MDL 100907, 201 impulsivity, 13 Mellaril (thioridazine), 85t NMDA receptor hypofunction affect, 46 MEM3454, 203 schizophrenia and, 11, 73, 74f memantine, 194 insomnia, memory, quetiapine for treating, 169 long-term formation, insulin, blocking M3-cholinergic recepters to BDNF and, 99 reduce, 146f mental retardation, 180 insulin resistance, 139 mesocortical dopamine neurons, 45 atypical antipsychotic agents and, 144f, 149f mesocortical dopamine pathway, 26f, 27, 29f psychopharmacologist options for, 151f and D2 antagonists, 85f quetiapine and, 169 dopamine output and, 120f, 132f risperidone and, 167 and serotonin-dopamine antagonism, 113f ziprasidone and, 171 to ventromedial prefrontal cortex, 30f zotepine and, 172 mesocortical prefrontal cortex integrated dopamine hypothesis of and emotion and cognitive symptoms, 17f schizophrenia, 33, 35f and schizophrenia symptoms, 15 interpersonal functioning, impaired, in mesolimbic circuits schizophrenia, 78 malfunctioning, and positive symptoms of inverse agonists, schizophrenia, 15, 16 vs. antagonists, 105 and positive symptoms of schizophrenia, 17f

226 Index

mesolimbic dopamine hypothesis, 28f n-back test, 74f mesolimbic dopamine pathway, 26, 26f, 27f, in schizophrenia, 75f 29, 44f N-methyl-d-aspartate (NMDA) glutamate blockade of D2 receptor antagonists, 84, 84f, system, development abnormalities, 28 91 N-methyl-glycine, 196 blockade of D2 receptors, 83 N-methyl loxapine, 173 dopamine output and, 120f, 132f Navane (thiothixene), 85t hyperactivity of, 35f nefazodone, 159 and thalamus, 51f Negative Symptom Assessment, 7t mesolimbic pathway, dopamine partial agonist negative symptom pharmacy, 181, 182f in, 130f nemonapride, 122f mesoridazine (Serentil), 85t neuregulin, 59, 64f metabolic highway, 142f genes coding for, 63f monitoring on, 149f, 150f and glutamate synapses strengthening, 66f metabolic pharmacy, 183, 185f and NMDA receptor regulation, 68f metabotropic glutamate receptors (mGluRs), and NMDA regulation, 71 39, 42f, 197 and synapse formation, 62, 65f mGluRs (metabotropic glutamate receptors), neurokinin antagonists, 203 39, 42f, 197 neurolepsis, 30, 82, 83, 150 mirtazapine, 200 neuroleptic-induced deﬁcit syndrome, 84 mitochondria, 61f neuroleptic-induced tardive dyskinesia, 31 modaﬁnil, 202 neuroleptic malignant syndrome, 96 molindone (Moban), 85t neuroleptics, 83 monoamine oxidase (MAO), neurons, and dopamine breakdown, 21, 21f cell death, 5HT2C receptors and, 103f excitotoxic mechanism and, 58f serotonin receptors and, 99 glutamate activity and, 55 mood stabilizers, 160, 180. See also lithium preventing in schizophrenia, 194 for aggression management, 181f dopaminergic, 20–22 for schizophrenia, 190 sensitivity to calcium, 59f adding to antipsychotic, 191f neuropsychological assessment batteries, 11 mesolimbic dopamine pathway role in, neurotensin antagonists, 204 26 neurotransmitters, reduction in, 5, 30 of cortical arousal, 152f motor activity glutamate as, 33 as antipsychotic side effect, 95 5HT6 receptors and, 103f disturbances, 2 nicotinic partial agonists (NPA), 203 dopamine and prevention of side effects, nigrostriatal dopamine pathway, 26f, 31, 32f 124 antipsychotic agent binding to postsynaptic nigrostriatal dopamine pathway to control, D2 receptors, 112f 31 and D2 antagonists, 86f muscarinic-1 agonists, 203 dopamine output and, 120f, 132f muscarinic-1 receptors and dopamine partial agonists (DPAs), 131f atypical antipsychotic agents and, 139f serotonin-dopamine interaction, 107f and sedation, 151f serotonin regulation of dopamine release, muscarinic 3 (M3) antagonism, and 108f antipsychotic agents, 147f NMDA (N-methyl-d-aspartate) antagonists, muscarinic cholinergic receptors, 194, 195f antagonism of, 144 NMDA (N-methyl-d-aspartate) receptors, 40, blockade from conventional antipsychotics, 40f, 41, 44f 92f, 91–95 enhancement of activity, 198f blocking to reduce insulin release, 146f excitation spectrum by glutamate, 57f antipsychotic agents and, 171 genes affecting, 58 myocarditis, clozapine and, 164 and glutamate systems, 37, 38f

Index 227

NMDA (N-methyl-d-aspartate) receptors M3 receptors blocked by, 146f (Contd.) pharmacological icon, 165f hypofunction, 200 potency, and dissociation, 125 hypofunction hypothesis of schizophrenia, raising levels of, 160f 44f, 45f, 69f, 70f, 72f for sedation, 185 and corticobrainstem glutamate pathways, and weight gain risk, 140t 42–45 OPC 4293, 129 hypofunction in glutamatergic corticostriatal oppositional defiant disorder, 179 and corticoaccumbens projections, 51f and schizophrenia symptoms, 15 long-term potentiation (LTP) triggered by, Org 24292, 200 66f Org 25271, 200 normal excitatory neurotransmission of, 56f Org 25501, 200 production, 37 Org 25573, 200 regulation of corticocortical glutamate osanetant (SR142801), 204 pathways, 53f requirements for active, 197, 197f paliperidone, 158, 159f, 160f, 167, 183 susceptibility gene regulation of, 71 pharmacological icon, 167f synapses with, 67f and sedation, 186f and synaptogenesis, 62 sedation risk with, 184 norepinephrine (NE). See also serotonin parabrachial nucleus (PBN) norepinephrine reuptake inhibitors dopamine pathway from, 26f, 33 (SNRIs) paranoia, 78 in arousal pathways, 150, 152f paranoid projection, 3 5HT2C receptors and, 103f paranoid psychosis, 3 norepinephrine reuptake inhibition (NRI), 174f drug-induced, 86 norepinephrine selective reuptake inhibitors dopamine agonists for treatment, 21 (NRIs), 202 nigrostriatal pathway dopamine deficiencies norepinephrine transporter (NET), and, 31, 32f inhibition, quetiapine for, 169 by norquetiapine, 169 vs. antagonists, 132f norfluoxetine, 159 perceptual distortions, 2 norquetiapine, 168, 168f periaqueductal gray matter, NRA0562, 122f dopamine pathway from, 26f, 33 nucleus accumbens, perospirone, 173 D2 receptor blockade in, 107 pharmacological icon, 173f as pleasure center, 83 perphenazine (Trilafon), 85t and schizophrenia symptoms, 16, 75, 76f pharmacodynamics, 156 “number needed to harm”, 87, 171 pharmacokinetics, 156 phencyclidine (PCP), obesity, and schizophrenia symptoms, 43, 44, 194 5HT2C receptors and, 103f Pick’s disease, cognitive symptoms, 13 atypical antipsychotic agents and, 137 pimozide (Orap), 85t blood pressure monitoring, 146 pipothiazine (Piportil), 85t peptide treatments for, 204 pituitary serotonin receptors and, 99 regulation of prolactin secretion, 116 observation, for negative symptom SPA action in, 131 identification in schizophrenia, 6, 8f pleasure olanzapine, 157, 157f, 164, 184 mesolimbic dopamine pathway role in, 26, 30 5HT6-antagonist properties of, 201 reduce ability to experience, 5 and antagonism of muscarinic cholinergic pleasure center receptor, 146f nucleus accumbens as, 83 and cardiometabolic risk, 140t PNU 9639/OSU 6162, 134f as CYP 2D6 substrate, 158, 159f polypharmacy, 190, 192f and diabetes, 171 Positive and Negative Syndrome Scale, 7t

228 Index

poststroke dementia, cognitive symptoms, 13 QTc prolongation, ziprasidone and, 171 pramlintide, 204 questioning, for negative symptom prefrontal cortex, identification in schizophrenia, 8f 5HT2A receptor activation, in schizophrenia, quetiapine, 136f, 158, 168, 183 114 5HT6-antagonist properties of, 201 fetal development, and schizophrenia, 57 binding properties, 168f and schizophrenia symptoms, 15, 75 and cardiometabolic risk, 140t SPA action in, 131 and diabetes, 171 presynaptic 5HT1A receptors, 102f dosage with carbamazepine, 161f, 162 presynaptic 5HT1B/D receptors, 101f pharmacological icon, 168f presynaptic antagonists, 199f potency, and dissociation, 124 presynaptic D2 receptors, 22, 23f, 24f for sedation, 185 procognitive agents, D1-selective agonists as, switching to nonsedating agent, 189 202 and weight gain risk, 140t prodrome negative symptoms, 6, 10f rapid dissociation, 119, 121, 122f, 124f amisulpride and, 177 rapid “off” time, 119 atypical antipsychotic agents and, 118f reasoning. See also cognitive functioning clozapine and, 163 distortions in schizophrenia, 78 conventional antipsychotic agents and, rebound psychosis, from discontinued 118f clozapine, 185 elevation, 90 relapse, inhibiting release, 32 after antipsychotic treatment, vs. side effects, inhibition by dopamine, 117f 95 olanzapine and, 165 remission quetiapine and, 169 by schizophrenic patient, 54 rise in levels, 88f resentment, 3 risperidone and, 167 retardation, 3 secretion regulation, 116 reward serotonin stimulation of, 117f blocking mechanisms, 84 zotepine and, 172 in mesolimbic dopamine system, 90 Prolixin (fluphenazine), 85t mesolimbic dopamine pathway role in, 26, 30 protease inhibitors, 159 RGH188, 134f glutamate for biosynthesis, 33 rimonabant, 203 psychosis, 1 risperidone, 166, 183 acute, ziprasidone for, 170 and cardiometabolic risk, 140t antipsychotic action to reduce symptoms, conversion to paliperidone, 159f, 160f 179 as CYP 2D6 substrate, 158, 159f as associated feature in disorders, 3t and diabetes, 171 disorders requiring presence as defining pharmacological icon, 166f feature, 2, 2t potency, and dissociation, 124 mesolimbic dopamine pathway role in, 26 raising levels of, 160f positive symptoms, 5t and sedation, 184, 186f quetiapine for, 169 for treating irritability, 181 rebound, from discontinued clozapine, 185 and weight gain risk, 140t psychotic depression, symptoms shared with RGS4 (regulator of G-protein signaling), 71 schizophrenia, 12, 13f genes for, 72f psychotic episode, 4 psychotic illness sarcosine, 196 combination chemotherapies for, 204 sarizotan (EMD128130), 134f, 202 misconceptions, 1 Scale for Assessment of Negative Symptoms, 7t pyramidal cells, scary faces, schizophrenic patient response to, malfunctioning glutamate input into, 52 77f, 78 output and input, 49 Schedule for the Deficit Syndrome, 7t

Index 229

schizoaffective disorder, risperidone effectiveness for, 167 symptoms shared with schizophrenia, 12, 13f stages, 55f schizophrenia substance abuse incidence in, 30 5HT2A receptors activation in prefrontal susceptibility genes for, 63t cortex, 114 symptoms, 11f, 2–18, 75 acquired vs. inherited, 56 overlap, 12f atypical antipsychotics to improve symptoms, shared with other illnesses, 12–18 109 treatment, vs. disease treatment, 179 best long-term outcomes, 154f, 155f ziprasidone for, 170 bifeprunox for treating, 178 schizophrenic patients cognitive symptoms, 13, 13t life expectancy of, 4 combination chemotherapies for, 204 siblings of, 74 diagnosis, value of deconstructing, 18 n-back test in, 76f excitotoxicity and, 56, 57f smoking and drug abuse by, 90, 203 fetal brain insult and, 57 suicide in, 4 free radical scavengers, 196f sedation, genetic basis, 58 antipsychotic agents and, 150–154 glutametergic treatments for, 196f avoiding, 152–153, 155f ideal treatment of, 112 long-term avoidance, 153f integrated dopamine hypothesis, 33, 35f, 88f quetiapine and, 169 and dopamine partial agonists, 132f receptors mediating, 151f and hit-and-run actions, 127f as short-term therapeutic tool, 152f and serotonin-dopamine antagonists, 121f vs. somnolence, 154f mesocortical dopamine hypothesis of zotepine and, 172 negative, cognitive, and affective sedation pharmacy, 184, 186f symptoms of, 31f seizures as more than psychosis, 3–7 clozapine or zotepine and increased risk, negative symptoms, 5, 5t, 6t 158, 164 causes, 14f zotepine and, 172 observation to identify, 6, 8f self-mutilation, 179 primary and secondary, 7t Serentil (mesoridazine), 85t in prodromal phase, 6, 10f serial learning, impaired, in schizophrenia, 11 questioning to identify, 8f d-serine, 195, 197, 197f reasons to measure, 7t production, 37, 38f, 39 scales for assessing, 7t d-serine racemase, 39 shared with other disorders, 12 l-serine, glycine synthesis from, 39 neurodegenerative hypothesis, 54f, 52–56 serotonin-2C antagonist, histamine-1 with, and neurodevelopmental hypothesis, 62f, 64f–67f appetite stimulation, 141f neuroimaging circuits in, 73 serotonin (5HT), 72f neutral stimuli and, 78f 1A agonists or antagonists, 201 NMDA receptor hypofunction hypothesis of, effect on gluatmate release, 115f 44f, 45f, 42–45, 52, 69f, 70f, 72f 5HT1D antagonist action by ziprasidone, 172 patient responsiveness to antipsychotic 5HT2A antagonist binding to 5HT2A treatment, 54 receptor, and dopamine release, 112 positive and negative symptoms, 4f and D2 antagonists, 119 positive symptom pharmacy, 179, 180f hyperprolactinemia reduction, 116 positive symptoms, 4, 5t reduction of positive symptoms, 116f link to mesolimbic/nucleus accumbens effect on gluatmate release, 115f area, 16 and positive symptoms improvment, shared with other disorders, 13f 113–116 presymptomatic and prodromal treatment, 5HT2A-selective antagonists/inverse 192, 193f agonists, 200 progressive nature of, 52 agonists or antagonists, 201 rapid clinical assessment, 9t functions, 103f

230 Index

olanzapine and, 165 pharmacological icon, 174f and weight gain, 137 and QTc prolongation, 171 5HT6 antagonists, physiological role, 201 siblings of schizophrenic patients, 74 5HT7 antagonists, 201 n-back test in, 76f 5HT21 receptors, agonism of, 135f sigma-1 agonists/antagonists, 200 dorsolateral prefontal cortex regulation by, 19f “sigma enigma”, 200 interaction with dopamine, in nigrostriatal skeletal muscle, insulin resistance in, 141, 144f dopamine pathway, 107f, 111f sleep production, 98f 5HT2A receptors and, 103f prolactin stimulation of, 117f quetiapine for improving, 168f regulation of dopamine release, 108f–110f serotonin receptors and, 99 synthesis and termination of action, 97 SLV313, 129, 134f, 202 termination of action, 99f SLV314, 129, 134f, 202 serotonin agonists, and 5HT2A antagonists, SM13493/lurasidone, 122f 132 CYP450 1A2 and, 158, 158f serotonin-dopamine antagonists (SDA), 96, by schizophrenic patients, 90, 203 97f, 121f, 180f somatodendritic autoreceptor, 98, 102f for aggression management, 181f somatodendritic dopamine D2 receptors, for cognitive function improvement, 182f 25f in development, 122f somnolence, vs. sedation, 154f for first-line treatment of schizophrenia spinophylin, genes for, 73f positive symptoms, 179 SR 147778, 203 integrated theory of schizophrenia and, 121f SR 241586, 204 and mesocortical dopamine pathway, 113f SR141716 A, 203 for negative symptoms in schizophrenia, 182f SR31742A, 200 new options, 200 SSR 146977, 204 switching to DPA, 190f SSR125047, 200 serotonin partial agonists (SPAs), 96, 136f SSR180711, 203 atypical antipsychotic agents and, 131 SSR181507, 134f, 202 serotonin receptors, 97, 100f, 105 SSR591813, 203 5HT1A and 5HT2A, 99 Stahl, S.M., Essential Psychopharmacology: The 5HT1A autoreceptors, 102f Prescriber’s Guide, 162, 163 5HT1A receptors, 105f Stelazine (trifluoperazine), 85t 5HT1B/D autoreceptors, 101f striatum, 5HT2A antagonist reduction of EPS, SPA action in, 131 105–107 stroke, 180 5HT2A receptors, 105, 105f, 106f excitotoxicity and, 56, 57f antagonist reduction of negative substance abuse. See also specific substance types symptoms, 108–112 incidence in schizophrenia, 30 5HT3 receptors, 103f substance P antagonists, 203 5HT6 receptors, 103f substantia nigra, 31 5HT7 receptors, 103f in schizophrenic patients, 4 postsynaptic, 97, 105 attempts, 179 impact of, 98 clozapine to reduce, 164, 183, 184f possible functions, 103f sulpiride (Dolmatil), 85t, 96, 129, 130, 134f, presynaptic, 97–105 135f, 177 serotonin selective reuptake inhibitors (SSRIs), clinical actions of, 125 110 pharmacological icon, 177f fluvoxamine, 159, 200 superiority, attitude of, 3 serotonin transporter (SERT), 97 susceptibility genes, 58 gene for, 73f for schizophrenia, 63t, 73 sertindole, 158, 173 switching antipsychotic agents, 185, 187f 5HT6-antagonist properties of, 201 process to avoid, 187f dosage with carbamazepine, 161f, 162 symptom domains, localization of, 15

Index 231

synapses, ventromedial prefrontal cortex (VMPFC), strength of, and survival or elimination, 67 dopamine deficit in mesocortical projections abnormal, 61 to, 28 genes causing, 65f, 66f mesocortical dopamine pathway to, 30f from gene expression, 58 and schizophrenia symptoms, 15, 76f verbal abuse, 179 talnetant, 204 verbal fluency, impaired, in schizophrenia, tandospirone, 201 11 tardive dyskinesia, 86, 87f, 95, 123f vesicular glutamate transporters (vGluT), 36f, clozapine and, 163 39, 40f neuroleptic-induced, 31 dysbindin regulation of, 71 reversal, 87 vesicular monoamine transporters (VMATs), from unwanted D2 receptor blockade, 136 and dopamine, 22f TC1827, 203 violence, 10 tension, 14 Vitamin E Tercian (cyamemazine), 85t, 96, 175 as free radical scavenger, 196f pharmacological icon, 175f vomiting terminal autoreceptor, 98 5HT3 receptors and, 103f thalamic dopamine pathway, 33 bifeprunox and, 178 thalamocortical glutamate pathways, 43f, 46 serotonin receptors and, 99 dopamine pathway to, 26f mesolimbic dopamine hyperactivity and, 50f waist circumference, monitoring, 146 sensory filter from GABA neurons, 46, 47f weight dopamine and, 48f baseline measurement, 149f sensory input inhibition from, 49f antipsychotic agents and, 143f thioridazine (Mellaril), 85t aripiprazole and, 176 thiothixene (Navane), 85t atypical antipsychotic agents and, 137, Thorazine (chlorpromazine), 82, 85t 140t tics clozapine and, 164 dopamine hyperactivity in nigrostriatal from histamine-1 receptor blockade, 95 pathway and, 31, 32f low risk antipscychotic agents, 140t TOH (tyrosine hydroxylase), 20, 20f monitoring, 150f tremor olanzapine and, 165 as antipsychotic side effect, 95 quetiapine and, 169 nigrostriatal pathway dopamine deficiencies ziprasidone and, 171 and, 31 zotepine and, 172 trifluoperazine (Stelazine), 85t worry, 14. See also anxiety triglycerides, elevated, atypical antipsychotic agents and, 144f Y931, 122f tryptophan, 97, 98f tryptophan hydroxylase (TRY-OH), 97, 98f ziprasidone, 136f, 158, 170, 183 tuberoinfundibular dopamine pathway, 26f, 32, with 5HT1D antagonist actions, 172 32f and cardiometabolic risk, 140t and D2 antagonists, 88f dosage with carbamazepine, 161f, 162 dopamine output and, 120f, 132f pharmacological icon, 170f hypoactivity of, 35f and sedation, 184, 186f tyrosine, 20, 20f and weight gain risk, 140t tyrosine hydroxylase (TOH), 20, 20f zotepine, 157, 157f, 158, 172 genes for, 73f 5HT6-antagonist properties of, 201 binding properties, 172f dosage with carbamazepine, 161f, 162 vabicaserin, 201 pharmacological icon, 172f varenicline, 203 and QTc prolongation, 171 dopamine pathway from, 26f, 33 zuclopenthixol (Clopixol), 85t

232 Index