Cambridge University Press 978-1-108-83857-3 — Stahl's Essential Psychopharmacology Stephen M

Cambridge University Press 978-1-108-83857-3 — Stahl's Essential Psychopharmacology Stephen M. Stahl Index More Information

Index

5HT. See serotonin AIMS (Abnormal Involuntary Movement amyotrophic lateral sclerosis, 353 scale), 174 analgesia, 380 ABC model of apathy, 536 akathisia, 166, 169 anatomical basis of neurotransmission, abstinence, 571–4 alcohol, 377, 553–6 1–5 acamprosate, 556 abstinence, 573 anesthesia, dissociative, 570 acetyl coenzyme A, 505 co-addictions, 553 anhedonia, 142, 162 acetylcholine, 5, 505–10 treatment of alcoholism, 556 antagonists, 41–3, 57, 58, 60, 62 dopamine and, 166 alcohol abuse, 378 alpha-1, 216, 225, 236, 327–8 acetylcholinesterase, 505 allodynia, 380 alpha-2, 309 acetylcholinesterase inhibition, 509–18 allopregnanolone, 320, 322 silent, 41, 42, 45, 192 action potential, 67, 73 allosteric modulation, 64–6, 261, 262 anticholinergics, 166, 168, 215, 294 active site, 45, 46 alogia, 142 anticonvulsants acute pain, 379, 380 alpha-1 antagonism, 216, 225, 236, 327–8 doubtful efficacy in bipolar disorder, addiction, 476, 539 alpha-2 adrenergic agonists, 481–4 352–3 behavioral, 575 alpha-2 antagonism, 309 insomnia treatment, 426 dopamine theory of, 542–3 alpha-2 autoreceptors, 254, 256, 258 mood stabilizers, 346 substance addictions, 544–75 alpha-2-delta ligands, 366, 377, 380 proven efficacy in bipolar disorder, adenosine, 440 pain alleviation, 398 347–51 ADHD (attention deficit hyperactivity SNRI combinations, 399 antidepressant actions, 195–234, 267, 283 disorder), 34, 449, 485, 539 alpha pore, 69, 70 antihistamines, 161, 215, 295, 425–6 comorbidities, 466, 480 alpha-synuclein, 493, 494 antipsychotic actions, 161–2, 242 neurodevelopment, 463–5 alternative splicing, 26 antipsychotics. See drugs targeting oppositional symptoms, 484 Alzheimer disease, 487–90, See also serotonin receptors, drugs targeting prefrontal cortex tuning, 454–63 dementia dopamine D2 receptors symptoms and circuits, 449–53 agitation in, 521–4, 528–33 anxiety, 78, 145, 359 treatments, future, 484 delusions in, 157 OCD and, 576 treatments, NET inhibitors, 480–4 dementia stage 3, 502 anxiety disorders, 196, 378 treatments, stimulants, 467–79 early detection, importance of, 497 ADHD and, 468 treatments, symptoms and, 466–7 impulsivity, 539 comorbidity, 360 advanced sleep phase disorder, 435, 437 MCI stage 2, 500–2 core symptoms, 360 affective blunting, 142 memory and cognition treatment, definition, 360 affective disorders, 244 509–18 major depression and, 360–2 affective symptoms, 95 Parkinson’s disease comorbidity, 494 MAOIs, 336 positive and negative, 278, 280, 306 pathology, 488 noradrenergic hyperactivity in, 370–2 schizophrenia, 145 presymptomatic stage, 499–501 overlapping symptoms of different, aggression, 145–7, 521, 577–8 psychosis in, 521–4 362–3 agitation, 145, 521–3 targeting amyloid, 496–9 pain disorders and, 387 dementia, 145, 157, 197 vascular dementia comorbidity, 492 psychotherapy, 359 glutamate target, 533 amantadine, 169 serotonin and, 368–70 neuronal networks of, 528–30 amisulpride, 205 treatment of, 377–8, 421 treatment, 523–4 amotivational syndrome, 563 anxiety phenotype, 363 treatment, multimodal monoamine, AMPA receptors, 101, 104, 330, 331 anxiolytic actions, 196, 366 530–2 amphetamine, 337, 356, 441–2, 472–6, apathy, 78, 536–7 agomelatine, 306–8 569 APOE4 gene, 497 agonist spectrum, 37, 43, 45, 56–62, 184, ADHD, 484 aripiprazole, 192, 229, 239, 326 192 formulations, 475 armodafinil, 442–4 agonists, 57, 58 isomers, 472 arousal, 457, 459 full, 37–41, 56, 192 amygdala, fear and, 364–5, 372, 374 arousal spectrum, 402 inverse, 42, 44–5, 61, 62, 240 amyloid cascade hypothesis, 496–9 asenapine, 220, 232 no agonist, 37 amyloid plaques. See beta-amyloid asociality, 142 partial. See partial agonists amyloid precursor protein, 497–8 asymptomatic amyloidosis, 499–501

615

INDEX

atomoxetine, 480–1 buspirone, 333, 370 closed state, 63 auditory hallucinations, 113 butyrylcholinesterase, 505, 510 clozapine, 217, 222–5 autoreceptors cocaine, 544, 545 alpha-2, 254, 256, 258 caffeine, 440–1 codeine, 559 monoamine, 8 calcium channel blockers (L-type), 352 cognition, Fab Four of, 317 avolition, 142 cannabidiol (CBD), 563, 565, 567 cognitive behavioral therapy, 374, 377, 576 axoaxonic synapses, 1, 3 cannabis, 150, 563–7 cognitive dysfunction axodendritic synapses, 1, 3 benefits and risks, 564 ADHD, 455, 456, 458 axosomatic synapses, 1, 3 side effects, 563 Alzheimer disease, 509–18 therapeutic uses, 564 chronic pain, 388 barbiturates, 556 carbamazepine, 350, 530 depression, 273 bath salts, 546 cardiometabolic risk, 196, 224 fibromyalgia, 390, 400 BDNF (brain-derived neurotrophic cardiometabolism, 198–201, 415 Parkinson’s disease, 493 factor), 266, 268, 329 cardiovascular disease, 156, 415, 432, sleep disorders, 402 behavioral addictions, 575 492, 524 sleep disturbance and, 414, 417 behavioral variant FTD, 494 carfentanil, 560 vortioxetine treatment, 315–17 benzodiazepine-insensitive GABAA cariprazine, 192, 231, 240, 328, 343–5 cognitive symptoms, schizophrenia, 95, receptors, 263–4 cataplexy, 434, 435, 446 144, 157 benzodiazepines, 321, 366, 377 catechol-O-methyltransferase, 253 competitive elimination, 151, 154 caution with, 378 central disorders of hypersomnolence, 432 compulsivity, 538–9, 571, 578 insomnia treatment, 421–2 central pain, 379 impulsive–compulsive disorders, benzodiazepine-sensitive GABAA central sensitization, 395 539–43, 575 receptors, 259–62 chemical neurotransmission, 1, 28 OCD, 295, 360, 576–7 beta-amyloid, 488, 496–8, 502 anatomical versus, 1–5 conceptual disorganization, 78 detection, 499, 501 epigenetics, 23–6 conditioned responses, 539 beta blockers, 375, 376 ion channels and, 73–6 conditioned stimuli, 539, 544 beta subunits, 68 mood disorders, 252–64 consolidation, 375 bifeprunox, 192 principles of, 5–9 constitutive activity, 37, 57 binge-eating disorder, 575 signal transduction cascades, 9–23, continuous positive airway pressure, 443 bipolar depression, 244 28, 53 controlled substance, 447 drug treatment, 236, 240 triggering gene expression, 18 cortico-brainstem glutamate pathways, 102 family history of, 250 ultradian sleep cycle, 414–16 cortico-cortical glutamate pathways, 105 first-line treatment, 342 chemotherapy, side effects, 309 cortico-striatal glutamate pathways, 104 identifying, 250 child abuse, 370 cortico-striato-thalamo-cortical (CSTC) missed or delayed diagnosis, 250 chlorpromazine, 161, 181, 201, 202 loops, 87, 362, 365–9 schizophrenia and, 249 choline, 505 cortico-thalamic glutamate pathway, 105 suicide rates, 251 cholinergic agonists, 242 CREB system, 15 versus unipolar, 249–51 cholinergic pathways, 509 criminogenic behavior, 146, 147 bipolar disorder chromatin, 23 cytochrome P450 (CYP450), 49–50, 323 anticonvulsants with proven efficacy, chronic back pain, 388 347–51 chronic pain, 379–400 daridorexant, 424 anticonvulsants with uncertain decreased gray matter, 387–90 DAT transporter. See dopamine efficacy, 352–3 duloxetine treatment, 302–3 transporters (DATs) bipolar I, 247 milnacipran treatment, 303 date rape drugs, 447, 559 bipolar II, 244, 247 targeting sensitized circuits, 395–9 delayed sleep phase disorder, 435, 437 combination treatments, 353 treatment, 390–400 delirium, 569 drug treatment, 338–58 circadian rhythm disorders, 430, 435–8 delusions, 77, 141, 524 blocking fear conditioning, 375–7 depression, 271–5 Alzheimer disease, 157 blonanserin, 234, 241 circadian rhythms, 307, 308 dementia, 521 brexanolone, 320 setting of, 275 Parkinson’s disease psychosis, 157 brexpiprazole, 192, 197, 230, 239, 327–8, circadian treatments, 438–40 dementia, 486, 537, See also Alzheimer 378, 530–2 circadian wake drive, 409, 412 disease bright light therapy, 438, 440, 444 citalopram, 295–6 agitation in, 145, 157, 197 buprenorphine, 560, 561, 562 classic neurotransmission, 6 apathy in, 536–7 bupropion, 306–8, 353–4, 480, 533 clock genes, 271 behavioral symptoms of, 521, 537 nicotine addiction, 551 clomipramine, 335 definition, 487 sertraline combination, 294 clonidine, 390, 482–3, 561 depression in, 534–5

616

Index

major causes of, 488–96 DNA methylation, 24 drugs targeting dopamine D2 receptors, psychosis in, 110, 134, 157, 521–3 donepezil, 510 159, 242 psychosis in, treatment, 523–7 DOPA decarboxylase, 253 agitation in dementia, 197 symptomatic treatments, 503–5 dopamine, 5 antidepressant actions, 195–234 dendrites, 2 acetylcholine and, 166 anxiolytic actions, 196 depression, 145, See also bipolar conversion to norepinephrine, 253 cardiometabolic actions, 198–201 depression, unipolar depression increase in prefrontal cortex, 299–302 first generation, 179–82, 201–3 affective symptoms, 278, 280 inefficient tuning of PFC by, 454–63 individual properties, 204–41 circadian rhythm disorder in, 271–5 projections, 279 mesocortical, 163 clinical effects of treatment, 284–5 release, 5HT2A regulation, 184–8 mesolimbic/mesostriatal, 161–3 dementia and, 534–5 synthesis, 79, 80 nigrostriatal, 165–81 drug side effects, 200 volume neurotransmission, 8 partial agonists, 189–92, 204–41 drug treatment, 229, 239 dopamine β-hydroxylase, 253 serotonin 2A and, 182–8 insomnia and, 418 dopamine blockers, 468 tuberoinfundibular, 164 See major depressive disorder. major adverse effects, 524 drugs targeting dopamine D3 receptors, depressive disorder bipolar disorder spectrum, 338–45 210, 240, 241 See major depressive episode. major dopamine D1 receptors drugs targeting serotonin receptors, 159, depressive episode drugs targeting, 204–41 243 See also mixed features of, 251 dopamine D2 receptors. drugs 1A receptors, 192–5, 207 monoamine hypothesis of, 264–5, 290 targeting dopamine D2 receptors 1B and 1D receptors, 214 monoamine receptor hypothesis of, pre- and postsynaptic, 228 2A receptors, 182–8 264–6, 267, 290 dopamine D3 receptors, 343–5 2C receptor, 211 mood stabilizer treatment, 288 drugs targeting, 210, 240, 241 3 receptor, 212 neuroplasticity and neuroprogression dopamine deficiency syndrome, 306 6 and 7 receptors, 213 hypothesis of, 266–76 dopamine hypothesis of psychosis, agitation in dementia, 197 serotonin or dopamine blockers in, 342 79–95, 110–14, 141 antidepressant actions, 195–234 symptom-based algorithm treatment, dopamine neurotransmitter network, anxiolytic actions, 196 280 79–91 cardiometabolic actions, 198–201 time course of effects of drugs, 266 classic pathways and key brain individual properties, 204–41 depression with mixed features, 248, 342 regions, 84 DSST (digital symbol substitution test), 317 depressive psychosis, 78, 157 mesolimbic pathway, 89, 542–3 dual orexin receptor antagonists descending spinal norepinephrine nigrostriatal pathway, 87–9 (DORAs), 423–4, 430 pathway, 390, 392 thalamic pathway, 85 duloxetine, 299, 302–3, 535 descending spinal serotonergic pathway, tuberoinfundibular pathway, 85 dynorphins, 390 390, 394 dopamine receptors, 81–5 dyslipidemia, 198 desensitization, 63, 64 dopamine theory of addiction, 542–3 dystonia, drug-induced, 166, 169 desvenlafaxine, 299, 302 dopamine transporters (DATs), 31, 80 deuteration, 175, 177, 354 ADHD treatment, 473–9 eating disorders, 293, 575 dextromethadone, 355–8 inhibition, 294, 333 Ecstasy, 358, 569 dextromethorphan, 306, 353–4, 533, 536 dopaminergic neurons, 79 empathogens, 569 diabetes, 198, 199, 415 dorsal anterior cingulate cortex (dACC), endocannabinoids, 6, 563, 564 diabetic ketoacidosis, 199, 200 450, 451 enkephalins, 390 Diagnostic and Statistical Manual of dorsal horn neurons, 382–4 entactogens, 569 Mental Disorders (DSM-5) dorsal horn, descending spinal synapses enzyme inhibitors, 45 ADHD, 463 in, 390–5 irreversible, 46 insomnia, 420 dorsal root ganglia, 380, 381 reversible, 47 major depressive episode, 245 dorsolateral prefrontal cortex, 387, 400, enzymes, 45–50 manic episode, 245 449 activity, 45 mixed features, 248 doxepin, 425, 427 epigenetics, 23–6 dietary tyramine interaction, 338 drug abuse, 447, 539 Epworth Sleepiness Scale, 430 diphenhydramine, 426 DAT occupancy and, 476, 479 escitalopram, 296 direct (go) dopamine pathway, 89, 90 reversal of habit, 571–4 esketamine, 331, 353, 571 disorganized/excited psychosis, 78 stimulants, 544–7 eslicarbazepine, 352 disorientation, 78 drug-induced dystonia, 166, 169 euphoria, 560 dissociation-assisted psychotherapy, 574 drug-induced parkinsonism, 165, 166–9, excessive daytime sleepiness. See dissociative anesthesia, 570 181 hypersomnia dissociatives, 569–71 drugs targeting dopamine D1 receptors, excitation–secretion coupling, 6, 8–9, disulfiram, 556 204–41 73, 75

617

INDEX

excitatory amino acid transporter, 96, 99 GABAA, benzodiazepine-insensitive, Parkinson’s disease psychosis, 157 excitement, 78 263–4 visual, 113, 524 executive dysfunction, 144, 449–50 GABAA, benzodiazepine-sensitive, hallucinogen-assisted psychotherapy, exposure therapy, 374, 378, 574, 576, 577 259–62 355–8, 376 extinction GABA transaminase (GABA-T), 258 hallucinogens, 135, 138, 567–9 fear, 373, 374–5, 574 GABA transporter (GAT), 34, 258 haloperidol, 181, 202, 204 pharmacological, 573 GABAergic drugs, 276 heroin, 559, 561, 573 extrapyramidal symptoms, 166 gabapentin, 352, 366, 395, 426 heteroreceptors, 125 galanthamine, 514 hippocampal-accumbens glutamate F17464, 241 gambling disorder, 575 pathway, 104 FDG PET, 490, 492, 502 gamma-hydroxybutyrate (GHB), 400, hippocampus, 372, 374 fear, 363–6 446–8, 559 histamine, 35, 402–6, 409 neurobiology of, 364–5 gene activation, 18, 19, 24, 25 histamine 1 antagonism, 425–6, 427 noradrenergic hyperactivity, 371 gene expression histamine receptors, 406 fear conditioning, 370–4 epigenetics, 23–6 histones, methylation, 23 blocking, 375–7 molecular mechanism, 18–23 homeostatic sleep drive, 408, 412 fear extinction, 373, 374–5, 574 neurotransmission triggering, 18 hormone-linked systems, 11, 12 fentanyl, 559 phosphoprotein triggering cascades, hostile belligerence, 78 fibro-fog, 390, 400 15–18 HPA (hypothalamic-pituitary-adrenal) fibromyalgia, 303, 387–9 gene silencing, 24, 25 axis, 266, 270 cognitive dysfunction, 388, 400 generalized anxiety disorder, 361, 377 human genome, 18 targeting ancillary symptoms, genetic testing, 323–5 Huntington’s disease, 28, 175 399–400 genetics hydrocodone (Vicodin), 559 treatment, 448 ADHD, 463 hyperactivity, 452, 454, 463 fight or flight response, 359, 364 schizophrenia, 148–50 hyperalgesia, 380 first messengers, 11, 13 genotyping, 50 hyperarousal, 418 flashbacks, 568 ghrelin, 415 hyperdopaminergia, 90, 92, 93 flumazenil, 263 glucose metabolism, 490 hyperglycemic hyperosmolar syndrome, fluoxetine, 293–4 glutamate, 5, 96 199, 200 olanzapine combination, 293, 326, agitation in Alzheimer disease, 533 hyperprolactinemia, 165, 187, 192 343 Alzheimer disease target, 515–18 hypersomnia, 402, 430–40 fluphenazine, 202, 203 key pathways in the brain, 102 causes of, 431–5 fluvoxamine, 295 synthesis, 96–7 treatment of, 440–8 forensic hospitals, 146, 147, 156 synthesis of GABA from, 255 hypervigilance, 402 frontotemporal dementias, 494–6 glutamate hypothesis of psychosis, hypnotic actions, 311 frontotemporal lobar degeneration, 494 95–114 insomnia treatment, 421–30 full agonists, 37–41, 56, 192 glutamate neurotransmitter network, hypnotics, sedative, 556 96–106 hypocretins, 406–11 G protein, 14 glutamate receptors, 99–105 hypodopaminergia, 95 G-protein-linked receptors, 36–45, 50 ionotropic, 54 hypomania, 248 agonist spectrum, 37, 43, 45 metabotropic, 100, 103 hypothalamic neurons, 407 agonists, 37–41 NMDA. See NMDA glutamate antagonists, 41–3 receptors idiopathic hypersomnia, 432, 433 inverse agonists, 42, 44–5 glutamate transporters, 34 illusions, 568 no agonist, 37 glutamic acid decarboxylase, 255 iloperidone, 225, 236 partial agonists, 41, 43–4 glycine transporters, 34 immediate early genes, 19, 20 structure and function, 36 glycine, synthesis, 97–9 impulse control disorders, 577–8 G-protein-linked systems, 11, 12, 13 Goldilocks solution, 43, 60, 191, 227, impulsive–compulsive disorders, 539 GABA (γ-aminobutyric acid), 5, 257–64, 428 binge eating, 575 349 grandiose expansiveness, 78 neurocircuitry of, 539–43 action termination, 258 gray matter, chronic pain, 387–90 impulsive violence, 147, 577 synthesis, 255 GSK-3 (glycogen synthase kinase), 48 impulsivity, 452, 454, 463, 538–9, 571, 578 GABA interneurons guanfacine, 482–3 inactivation state, 61, 63 5HT receptors on, 121, 125, 130 inattention, 449, 450, 451, 463 prefrontal cortex, 105–10 habit circuit, 544, 561, 571, 572 indirect (stop) dopamine pathway, 89, 90 GABA receptors, 258–64 habits, 538, 539, 576 inhalants, 547 GABAA, 321, 366, 421–3 hallucinations, 77, 113, 141, 435, 568 inherited disease, classic theory of, 148 GABAA receptor subtypes, 258–61 dementia, 521 insomnia, 311, 402, 418–20

618

Index

behavioral treatments, 430 mania monoamine oxidase inhibitors (MAOIs), diagnosis and comorbidities, 418–20 anticonvulsant treatment, 346 336–7, 377 treatment, 421–31 carbamazepine treatment, 350 bipolar depression, 342 insulin resistance, 197, 198, 200 drug treatment, 195 dietary tyramine interaction, 338 internet addiction, 575 lithium treatment, 345 drug–drug interactions, 338 interneurons, 380 mixed features of, 248, 251 subtypes, 337–41 inverse agonists, 42, 44–5, 61, 62, 240 mood stabilizer treatment, 288 monoamine projections, 279 ion-channel-linked systems, 11, 12 serotonin and dopamine blockers in, monoamine receptor hypothesis of ion channels, 76 338, 342 depression, 264–6, 267, 290 ligand-gated. See ligand-gated ion valproate treatment, 349 monoamine transporters, 30, 31–4, 208 channels manic episodes, 245, 277, 278 unipolar depression, 285–8 neurotransmission and, 73–6 MAOIs. See monoamine oxidase mood disorders, 244, 282, See also mania, voltage-sensitive. See voltage-sensitive inhibitors depression ion channels mazindol, 485 description of, 244–52 ionotropic glutamate receptors, 54 MDMA, 356, 376, 378, 569–71 future treatments for, 353–8 iproniazid, 336 assisted psychotherapy, 574 mixed features of, 248, 251–2 irreversible enzyme inhibitors, 46 MDPV, 546 neurobiology of, 252–76 medication-assisted therapy, 561 pain disorders and, 387 kainate receptors, 101, 104 melatonergic agents, 439, 440 symptom-based treatments, 279–82 ketamine, 106, 328–32, 353, 376, 569–71 melatonin, 275, 439, 440 symptoms and circuits in, 277–82 ketamine-assisted psychotherapy, 574 melatonin receptors, 306 mood episodes, 246 kinase, third messenger, 14, 16 memantine, 520, 521–4, 533 mood related psychosis, 157 memory difficulties, 316 mood spectrum, 244–9 lamotrigine, 350–1 Alzheimer disease, 509–18 mood-stabilizers, 288, 345–6 late genes, 20, 22 memory, traumatic, 356, 366, 375, mood-stabilizing action, 283 lemborexant, 423 574 morphine, 559, 561 leptin, 415 mesocortical dopamine pathway, 95 motivation, lack of, 536 leucine zippers, 19, 20, 21 mesocortical hypodopaminergia, 95 motor disturbances, 78 levodopa, 170 mesolimbic dopamine pathway, 89, motor side effects, 165–81 levomilnacipran, 300, 303 542–3 partial agonists, 192 Lewy bodies, 157 mesolimbic hyperdopaminergia, 90 mu-opioid receptors, 390, 556 Lewy body dementias, 492–5 mesostriatal hyperdopaminergia, 93 multimodal monoamines, 530–2 licarbazepine, 352 messenger RNA (mRNA), 26 Multiple Sleep Latency Test, 431 ligand-gated ion channels, 51–66, 76 metabolic highway, 198, 199, 201 muscarinic receptors, 506–7 agonist spectrum, 56–62 metabolic monitoring, 196, 199 allosteric modulation, 64–6 metabolic toolkit, 201 nalmefene, 556, 573 different states of, 61–4 metabotropic glutamate receptors, 100, naloxone, 560 gatekeeper, 52 103 naltrexone, 306, 556, 561, 563, 573, 575 pentameric subtypes, 53 metformin, 201 NAMs (negative allosteric modulators), structure and function, 53 methadone, 355, 559, 560, 561, 562 64–6 tetrameric subtypes, 54–5 methylation, 23, 24 narcolepsy, 407, 430, 433, 435, 443, 444, lisdexamfetamine, 473, 575 methylphenidate, 441–2, 469–72, 484 446 lithium, 48, 332, 345–6 formulations, 470 nausea and vomiting, 309 local anesthesia, 380 mianserin, 309 n-back test, 449, 451 lofexidine, 561 microRNA (miRNA), 27 nefazodone, 311 long-term potentiation, 151 migrants, 150 negative affect, 278, 280 LSD, 358, 568 mild cognitive impairment, 487, 490, negative feedback regulatory signal, 255 lumateperone, 227, 237–9 493, 500–2 negative symptoms, 95, 142–4, 156 lurasidone, 226, 236, 343 milnacipran, 300, 303 secondary, 162–3 mirtazapine, 232, 308–13, 333 NET transporters. See norepinephrine magic mushrooms, 358 mixed dementia, 495 transporters (NETs) magnesium, 104 mixed features, 248, 251–2 neuroactive steroids, 320–5 magnetic resonance imaging, 491 modafinil, 333, 442–4 neurobiology major depressive disorder, 246, 252 Molly, 358, 569 mood disorders, 252–76 anxiety disorder and, 360–2 monoamine autoreceptors, 8 sleep and wakefulness, 402–15 core symptoms, 360 monoamine hypothesis of depression, neurodevelopment, 151, 152 major depressive episode, 248, 277 264–5, 290 ADHD, 463–5 symptoms and circuits, 277 monoamine oxidase (MAO), 253 schizophrenia, 151–3

619

INDEX

neurofibrillary tangles, 488, 502, 503 projections, 279 Alzheimer disease comorbidity, 494 neuroinflammation, 270 synthesis, 252 cognitive dysfunction, 493 neuroleptic-induced deficit syndrome, norepinephrine–dopamine reuptake Parkinson’s disease dementia, 492–5 162 inhibitors (NDRIs), 303–6, 333 Parkinson’s disease psychosis, 78, 133, neuroleptic malignant syndrome, 169 norepinephrine receptors, 254–6, 258 136, 139, 157, 524 neuroleptics, 162 norepinephrine transporters (NETs), paroxetine, 294, 295 neuronal cell loss, 488, 490, 491 31, 254 partial agonists, 41, 43–4, 57–61, 189–95, neurons, 1, 2 norepinephrine transporter (NET) 204–41 general structure, 2 inhibition, 294, 298–303, 370 Pavlov’s dogs, 370 neuropathic pain, 380, 382–90, See also ADHD, 480–4 pentameric ligand-gated ion channels, 53 fibromyalgia norquetiapine, 227 perceptual distortions, 78 central mechanisms, 382–6 NRX101, 237 periaqueductal gray, 390 peripheral mechanisms, 382 NSAIDs (nonsteroidal anti-inflammatory peripheral pain, 379 neuropathic pain syndromes, 380 drugs), 382 perospirone, 233, 241 neuropeptides, 35 nucleosomes, 23 PET scans neuroplasticity and neuroprogression nucleus accumbens, 162 beta-amyloid, 499, 501 hypothesis of depression, 266–76 FDG PET, 490, 492, 502 neurotransmission, 1, See also chemical obesity, 198, 415, 575 pharmacodynamics, 49 neurotransmission obsessive–compulsive disorder (OCD), pharmacokinetics, 49 anatomical basis of, 1–5 295, 360, 576–7 hypnotic actions, 426–30 neurotransmitters, 5–6 obstructive sleep apnea, 430, 431, 434, pharmacological extinction, 573 enzymes as. See enzymes 443 phasic dopamine system, 455 psychosis pathways, 79 olanzapine, 218, 225 phasic inhibition, 259 transporters. See transporters fluoxetine combination, 293, 326, 343 phencyclidine, 106, 569–71 neurotrophic factors, loss of, 266, 268 ondansetron, 556 phosphatase, third messenger, 15, 16 neurotrophin-linked systems, 11, 12 OPC4392, 193 phosphoprotein cascades, 15–18 neutropenia, 224 open state, 63 phosphoprotein messenger, 13–15 NGF (nerve growth factor), 6 opiates, 559 pimavanserin, 231, 240, 526 nicotine, 63, 466, 547–53 opioid use disorder, 355 pitolisant, 444 alternative forms of delivery, 551 opioids, 375, 390, 556, 559 plasma membrane transporters, 30 treatment of addiction, 548–53 abstinence, 573 polygenic risk score, 150 nicotinic receptors, 506, 507–9, 548 addiction, 559–60 polysomnography, 420, 431 nigrostriatal dopamine pathway, 87–9 addiction, treatment of, 560–2 positive affect, 278, 280, 306 nitric oxide, 6 endogenous neurotransmitter system, positive symptoms, 90, 141, 156 nitric oxide synthase, 295 559 psychosis, 92–3 NMDA antagonism, 328, 330, 355 orbital frontal cortex, 454 postsynaptic dopamine receptors, 81 NMDA glutamate hypofunction orexin, 409, 435 posttraumatic stress disorder (PTSD), hypothesis of psychosis, 105–14 dual orexin receptor antagonists, 360, 362 NMDA glutamate receptors, 97–101, 104 423–4, 430 drug treatment, 196 histamine at, 406 orexin receptors, 407 fear conditioning, 372 hypofunction, 111, 114 orexins, 406–11 treatments for, 377, 568, 574 NMDA receptor activation, 375 oxcarbazepine, 352 prazocin, 370 nociception, 380, 381 oxycodone (OxyContin), 559 predementia AD, 500–2 pain pathways, 396 prefrontal cortex nociceptive nerve fibers, activation, 381 pain, 379–84, See also chronic pain disorder of the, 449–53, 463 nociceptive pathway, 381 definition, 380 dopamine neurotransmission, 8 from the spinal cord to the brain, in dementia, 537 dorsolateral, 387, 400, 449 382–4 mood and anxiety disorders and, 387 GABA interneurons, 105–10 to the spinal cord, 381–2 paliperidone, 223, 235 increased dopamine in, 299–302 non-24-hour sleep–wake disorder, 437, PAMs (positive allosteric modulators), inefficient tuning of, 454–63 438 64–6, 421–3 ventromedial, 372, 374 non-REM sleep, 413, 414 panic attacks, 361, 377, 569 pregabalin, 352, 366, 395, 426 noradrenaline. See norepinephrine panic disorder, 361, 372, 377 presymptomatic stage of Alzheimer noradrenergic hyperactivity, 370–2 paralytic ileus, 167, 183 disease, 499–501 norepinephrine, 5, 252–6, 370 paranoid psychosis, 78 presynaptic dopamine receptors, 81, 82 action termination, 253 parkinsonism, drug-induced, 165, 166–9, primary afferent neurons, 380, 381 inefficient tuning of prefrontal cortex 181 primary transcript, 26 by, 454–63 Parkinson’s disease, 338 prisons, 146, 156

620

Index

processing speed, 317 PTSD. See posttraumatic stress disorder nature and nurture of, 149 prodromal negative symptoms, 143 (PTSD) negative symptoms, 95, 142–4, 156 proinflammatory molecules, 270 neurodegeneration and, 154–6 projection neurons, 380 quetiapine, 219, 220, 227–32, 326, 343 neurodevelopment and, 151–3 prolactin levels, 164, 187, 193 quinidine, 353–4, 534, 536 NMDA receptor hypofunction, 111, 114 pseudobulbar affect, 535 positive symptoms, 141, 156 psilocin, 568 radafaxine, 304 positive symptoms of psychosis in, 92–3 psilocybin, 358, 376, 568, 569 ramelteon, 439 second messenger assisted psychotherapy, rasagiline, 338 forming, 11–14 psychedelic experience, 568 rashes, 352 to phosphoprotein cascades, 15–18 psychiatric vital sign, 381, 399, 401 receptor tyrosine kinases, 48 to phosphoprotein messenger, 13–15 psychic pain, 302 reconsolidation, 374, 375, 376, 574 secondary negative symptoms, 162–3 psychomotor retardation, 78 recurrence in depression, 284 sedation, 197, 202 psychopathic violence, 147, 577 reduced positive affect, 280, 306 sedative hypnotics, 556 psychosis, 77, 158, See also schizophrenia relapse, 571 segmental central sensitization, 384 cannabis and, 563 in depression, 284, 286 selegiline, 337, 338 dementia, prevalence in, 521 REM sleep, 413, 414, 435 SEP-363856, 242 dementia-related, 110, 134, 157, 521–3 remission in depression, 284, 286 serine, synthesis, 97–9 dementia-related, treatment of, 523–7 repetitive transcranial magnetic serious mental illness (SMI), 156 depressive, 78, 157 stimulation (rTMS), 577 serotonergic hypnotics, 424–5 dopamine hypothesis of, 79–95, reserpine, 174 serotonin, 5, 113 110–14, 141 response in depression, 284 anxiety and, 368–70 drug treatment. See drugs targeting resting state, 57, 61, 63 dementia-related psychosis, 524–7 serotonin receptors, drugs targeting retrograde neurotransmission, 6–7 neuronal network, 121 See also dopamine D2 receptors reuptake pumps, 174, projections, 279 glutamate hypothesis of, 95–114 transporters synthesis and termination of action, mood-related, 157 reversible enzyme inhibitors, 47 114–15 neurotransmitter pathways, 79 reward, 542, 544 serotonin antagonist/reuptake inhibitors other psychotic disorders, 156–8 reward conditioning, 545 (SARIs), 311–16 paranoid, 78 reward pathway, 572 serotonin blockers Parkinson’s disease. See Parkinson’s rheostat analogy, 43 bipolar disorder spectrum, 338–45 disease psychosis ribosomal RNA (rRNA), 27 serotonin hyperfunction hypothesis of positive symptoms of, 90, 92–3 riluzole, 352 psychosis, 131–41 serotonin hyperfunction hypothesis risperidone, 222, 234, 235 serotonin hypothesis of psychosis, of, 131–41 rivastigmine, 510–16 111–41 serotonin hypothesis of, 111–41 RNA, 26–7 serotonin network, 113–33 symptoms of, 77–8 RNA interference, 26 constructing, 119–21 psychotherapy roluperidone, 235, 241 serotonin partial agonist reuptake anxiety disorders, 359 inhibitor (SPARI), 296–9 cognitive behavioral therapy, 374, safinamide, 338 serotonin receptors. See also drugs 377, 576 SAGE-217, 322 targeting serotonin receptors dissociation-assisted, 574 salivation, excessive, 224 5HT1A, 116, 118, 121, 296–9, 317 hallucinogen-assisted, 355–8, 376 samidorphan, 201 5HT1B, 125, 318 ketamine-assisted, 574 schizoaffective disorder, 249 5HT1B/D, 118, 119, 318 See also MDMA-assisted, 574 schizophrenia, 141, 156, 5HT2A, 125 psilocybin-assisted, 574 psychosis 5HT2A, dopamine release regulation, PTSD, 378 affective symptoms, 95, 145 184–8 psychotic violence, 146, 577 aggressive symptoms, 145–7 5HT2A, hyperactivity/imbalance, psychotomimetic experience, 569 bipolar disorder and, 249 111–41 psychotropic drugs cognitive symptoms, 95, 144, 157 5HT2B, 117, 119 enzymes as targets of, 45–50 dopamine hypothesis of psychosis in, 5HT2C, 125, 293–4 G-protein-linked receptors as targets, 92–5 5HT3, 125–9, 309–13, 318 See 36–45, 50 drug treatment. drugs targeting 5HT6, 130 ion channels as targets of, 51–76 serotonin receptors, drugs targeting 5HT7, 130–3, 318–24 molecular targets, 29 dopamine D2 receptors overview, 114 nomenclature, 29 future drug treatment, 241–2 serotonin transporters (SERTs), 31, 33 transporters as targets, 29–35, 50 genetics and, 148–50 inhibition of, 289, 296, 317, 318–24 life expectancy, 156 sertindole, 232, 240

621

INDEX

sertraline, 294, 378 clinical uses of, 289 topiramate, 201, 352, 556, 575 setiptiline, 309 common features of six drugs, 289–92 trace amines, 241–38 shift work disorder, 435, 436, 444 depression in dementia, 534 tradozone, 311–15, 424–5 sigma-1 binding, 294, 295 OCD, 577 transduction, 381 signal propagation, 74 triple-action combo, 333 transfer RNA (tRNA), 27 signal transduction cascades, 9–23, 28, unique properties of six drugs, 292–3 transporters, 29–35, 50 53 stabilizers. See partial agonists classification and structure, 29–31 four important types of, 11, 12 steroids, neuroactive, 320–5 histamine and neuropeptides, 35 second messenger, forming, 11–14 Stevens Johnson syndrome, 352 monoamine, 30, 31–4, 208 second messenger, to phosphoprotein stigma, 145 SLC1 gene family, 31 cascades, 15–18 stimulants, 467–79, 544–7 vesicular, 32, 35 second messenger, to phosphoprotein atypical, 546 tranylcypromine, 337 messenger, 13–15 slow release vs. fast release, 478–9 traumatic memories, 356, 366, 375, 574 time course, 11 targeting DATs, 473–8 trazodone, 535 silent antagonists, 41, 42, 45, 192 treatment of addiction, 547 treatment responsiveness, 155 Sinclair method, 573 stimulus-response conditioning, 571 tricyclic antidepressants (TCAs), 333–7 SLC1 gene family, 31, 35 strengthening, synapse, 151, 154 triglyceride levels, 197, 198, 199 SLC17 gene family, 31, 35 stress, ADHD, 467, 469, 480 tryptophan, 114 SLC18 gene family, 31, 35 stroke, 492, 524 tuberoinfundibular dopamine pathway, SLC32 gene family, 31, 35 Stroop test, 450, 451 85 SLC6 gene family, 30, 31–5 subjective memory complaints, 487, 488 tuberomammillary nucleus, 406, 408 sleep sublingual formulation, 232 type 2 diabetes, 415 neurobiology of, 402–15 substance addictions, 544–75 tyramine, 338 purpose of, 414–15 substrates, 45, 46 tyrosine, 80, 252 REM and non-REM, 413, 414, 435 suicide, 145, 156 tyrosine hydroxylase, 253 sleepiness, 430–4 clozapine treatment, 223 sleep/wake cycle, 412–13 depressed patients, 251 ultradian sleep cycle, 413–16 disturbance of, 414, 416 mixed feature patients, 251 unipolar depression, 34, 244 small interfering RNA (siRNA), 27 prevention, 346 augmenting strategies for, 325–35 small nuclear RNA (snRNA), 27 suicide inhibitors, 46 drugs for, 289–325 smoking, 476, See also nicotine sulpiride, 202, 205 monoamine reuptake blockers, 285–8 cessation, 306, 573 supersensitivity, 170, 171 or bipolar, 249–51 snare proteins, 73 suprachiasmatic nucleus, 275, 307 second-line monotherapies, 333–8 SNRIs (serotonin–norepinephrine suprasegmental central sensitization, treatment resistance in, 323–38 reuptake inhibitors), 298–303 384, 390 α2δ ligand combinations, 399 suvorexant, 423 valbenazine, 177 anxiety disorders, 368 synapses, 1, 3 valproic acid (valproate), 347–50 arousal combo, 333 enlarged, 5 varenicline, 551, 552, 573 mirtazapine combination, 333 synaptic neurotransmission, 4 vascular dementia, 491–2, 534 pain treatment, 380 synaptogenesis, 151, 154 VEGF (vascular endothelial growth triple action combo, 333 factor), 329 social anxiety disorder, 362, 372, 377 tardive dyskinesia (TD), 166 venlafaxine, 299, 302 sodium oxybate, 446–8 pathophysiology, 170–4 ventromedial prefrontal cortex, 372, 374 sodium potassium ATPase (sodium treatment, 174–81 vesicular transporter for glutamate, 99 pump), 32, 33 tasimelteon, 439 vesicular transporters, 31, 32, 35 sodium valproate, 347–50 tau protein, 488, 494, 502, 503 VIAATs (vesicular inhibitory amino acid solriamfetol, 444 tetrabenazine, 175–6 transporters), 255 soma, 2 tetrahydrocannabinol (THC), 563, 565, vilazodone, 296–9 somatic pain, 302 567 viloxazine, 485 somatosensory cortex, 380 tetrameric ligand-gated ion channels, violence, 145–7, 575, 577–8 specific neutral amino acid transporters 54–5 visual hallucinations, 113, 524 (SNATs), 96 thalamic dopamine pathway, 85 vital sign, 381, 399, 401 spinobulbar tracts, 380 thalamo-cortical glutamate pathway, 104 VMAT1, 174 spinothalamic tract, 380 third-messenger kinase, 14, 16 VMAT2 inhibition, 174–81 SSRIs (selective serotonin reuptake third-messenger phosphatase, 15, 16 VMAT2 transporter, 31, 81, 254 inhibitors), 289–96 thyroid, 333 VMATs (vesicular monoamine anxiety disorders, 368 tonic inhibition, 259, 263 transporters), 35

622

Index

voltage-sensitive calcium channels wake-promoting agents, 440–8 xanomeline, 242 (VSCCs), 70–3, 366, 395 wakefulness, neurobiology of, 402–15 voltage-sensitive ion channels, 66–73, 76 weight gain, 198, 224 Z drugs, 425–6 structure and function, 66 widespread pain index (WPI), 387 ziprasidone, 224, 236 voltage-sensitive sodium channels withdrawal syndrome, 546, 560 zolpidem, 423 (VSSCs), 67–70, 347, 350, 351, 381 worry, 362, 363 zopiclone, 423 volume neurotransmission, 6–9 neurobiology of, 365–9 zotepine, 221, 233 vortioxetine, 311, 315–20, 535 noradrenergic hyperactivity, 372

623