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Cambridge University Press 978-0-521-71412-9 - Depression and Bipolar Disorder: 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.

5HIAA (5-hydroxy-indole acetic acid), alpha 2 antagonists 31 icon, 107f in cerebrospinal ﬂuid, 36 and norepinephrine, 108f “able stabilizers”, 265, 265f and serotonin, 108f, 109f acamprosate as serotonin norepinephrine disinhibitors, 106, in combos for bipolar disorder, 263 110f acetylcholine receptors, TCA and, alpha 2 delta ligands, 236 150f alpha 2 receptors activity-dependent spine formation, by on axon terminal, 26f estradiol, 162f blockade of, 107f adatanserin, 122 somatodendritic, 23, 27f adolescence alpha-L-glutamyl transferase, 175 antidepressants for, 67f alprazolam (Xanax) mania in, 260 and CYP 450 3A4, 156 affective disorders, 2. See also mood and sedation, 157 disorders ALS (amyotrophic lateral sclerosis) affective spectrum disorders, 104 riluzole for, 233f norepinephrine and, 94 amantadine “affective storms”, in children, 260 for bipolar disorder, 243 aggressiveness, 252f icon, 244f Agilect/Azilect (rasaligine), 127t mechanism of action for Parkinson’s disease, 130 on GABA, glutamate, sigma, and agitation, 95 dopamine, 224t agomelatine (Valdoxan), 122, 206 VSSCs, synaptic vesicles, and carbonic icon, 209f anhydrase, 223t agoraphobia, in children, 261 possible actions in bipolar disorder, 246f akathisia putative clinical actions, 221t, 222t from paroxetine withdrawal, 85 amibegron, 210 from SSRIs, 78 amitriptyline (Elavil, Endep, Tryptizol, Loroxyl), alertness, 198 120, 145t loss amoxapine (Asendin), 120, 145t bupropion for, 104 amphetamines, 124, 127t as SSRI side effect, 78 action alpha 1 adrenergic receptors MAO inhibitors with, 127t TCA and, 147, 151f with MAOIs, and hypertension, 141t

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© Cambridge University Press www.cambridge.org Cambridge University Press 978-0-521-71412-9 - Depression and Bipolar Disorder: Stahl’s Essential Psychopharmacology, Third Edition Stephen M. Stahl Index More information

amygdala interaction with MAOIs, 143t and anxiety/fear, 252f “intramolecular polypharmacy” of, 90 beta-3 receptors in, 211 manic or hypmanic episode on, 11 and depressed mood, 38 L-5-methyltetrahydrofolate (MTHF) and, impact on suicidal ideation, 41 179f information processing monoamine oxidase inhibitors (MAOIs), and depressed mood, 40f 122–145 manic episode symptoms linked to, 54 norepinephrine and dopamine reuptake noradrenergic receptor stimulation in, 95 inhibitors (NDRIs), 100–104. See also amyotrophic lateral sclerosis (ALS) norepinephrine dopamine reuptake riluzole for, 233f inhibitors (NDRIs) anorexia, fluoxetine for, 81 over life cycle, 67, 67f anticonvulsants. See also specific agents pharmacokinetics, 151 carbamazepine (Equetro), 226 prior responses to, and bipolar diagnosis, as mood stabilizers, 220 18 gabapentin, 235 putative mechanisms, 81t lamotrigine, 230–234 response rates, 62f levetiracetam, 237 risks of use or avoidance during pregnancy, oxcarbazepine/eslicarbazepine, 229 166t pregabalin, 235 risks to fetus, 166 riluzole, 234 role in bipolar disorder, 247 topiramate, 234 serotonin norepinephrine reuptake inhibitors zonisamide, 235 (SNRIs), 89. See also serotonin valproic acid, 220 norepinephrine reuptake inhibitors antidepressant “poop out”, 9 (SNRIs) antidepressants. See also heroic combos; serotonin suicidality in adolescent females, 165 norepinephrine reuptake inhibitors symptoms persisting after treatment with, (SNRIs) 64 bipolar depression response to, 20f time course of effects, 69f brain MAO-A inhibition for efficacy, 127 trimonoaminergic modulators (TMMs) and, in clinical practice, 187 158 cost-based algorithm, 190, 190f triple-action combo, 205 evidence-based algorithm, 189f two mechanisms vs. one, 90, 90f evidence-based selections, 189 antipsychotic agents reduced positive affect vs. increased negative as antidepressants, 206 affect, 191 anxiety selection process, 187 amygdala and, 252f symptom-based algorithm, 193f, 195f, 196f, gabapentin for, 236 197f pregabalin for, 236 symptom-based selection, 191, 192f reduced, 197 clinical trials, 62 anxiety disorders combinations for major depressive disorder, in children, 261 199 fluvoxamine for, 85 combinations for unipolar depression, 200f MAO inhibitors for, 123 continuation, 63f NET inhibition and, 106 CYP450 2D6 impact on plasma levels, 155 paroxetine for patients with, 84 delay in relief from depression, 76f venlafaxine for, 97 in development, 206t, 207t apathetic recovery, 78, 94 targeting neurokinins, 208t apathetic temperament, 8f targeting novel sites of action, 208t apathy effectiveness in clinical practice, 62 circuits, 41f general principles, 60–68 in depression, 39 impact on mixed states of depression and appetite mania, 15 changes in, 41 increase in monoamines, 68f circuits, 46f

280 Index

appetite suppressants, interaction with MAOIs, symptoms, 19f 143t vs. unipolar depression, 16, 17t, 18, 18f aripiprazole impact of antidepressant treatment on actions as mood stabilizer, 241f unrecognized, 16 in combos for bipolar disorder, 261, 265, 265f pharmacological mechanisms to achieve pharmacological actions, 241f remission, 253 arousal combos, 206 postpartum, 167 asenapine, 107f progressive nature of, 21f Asendin (amoxapine), 120, 145t rapid cycling, 6f atomoxetine, 105, 152, 154f residual symptoms after first-line treatment, CYP450 2D6 impact on plasma levels, 155 250–258 atorvastatin spectrum, 9, 9f,15 and CYP 450 3A4, 156 treatment, 2, 3f risk of muscle damage, 157 amantadine for, 243 attention deficit hyperactivity disorder (ADHD) benzodiazepines for, 242 atomoxetine for, 105, 106 calcium channel blockers for, 245 mania vs., 260, 261 inositol for, 247 atypical antipsychotic agents ketamine for, 243 in bipolar depression, 240f memantine for, 243 pharmacological actions, 241f L-methylfolate (Deplin) for, 247 for mania, actions, 239f with mood stabilizer, 216 for mania and bipolar depression, mechanism omega-3 fatty acids for, 246 of action, 238 thyroid hormones for, 247 as mood stabilizers, 242f unstable and excessive neurotransmission, for nonpsychotic mania symptoms, 237 254f autoreceptors, 23 and women, 258 axon terminals. See also presynaptic axon terminals Bipolar I disorder, 4, 5f alpha 2 receptors on, 26f bipolar I 1/2 disorder, 11f Azilect/Agilect (rasaligine), 127t Bipolar II disorder, 4, 7f for Parkinson’s disease, 130 bipolar II 1/2 disorder, 11, 12f bipolar III disorder, 11, 12f basal forebrain Bipolar III 1/2 disorder, 11, 13f inefficient information processing, and sleep Bipolar IV disorder, 13, 14f disturbances, 51f ”bipolar storm”, 252, 254f and sleep disturbances, 39, 42f Bipolar V disorder, 13, 14f benzodiazepines Bipolar VI disorder, 15, 15f for bipolar disorder, 242 blood pressure in combos for bipolar disorder, 263 noradrenergic receptor stimulation and, 95 beta 3 agonists, as antidepressants, 206, 210, 211f tyramine and, 130, 137 beta 3 receptors, 210f BMS181, 101, 122 beta blockers bone marrow, carbamazepine impact, 227 and CYP450 2D6 inhibitors, 156 Boston bipolar brew, 263, 264f bicifidine, 100, 100f brain. See also circuits bipolar 1/2 disorder, 9, 10f activity in depression, 38 bipolar 1/4 disorder, 9, 10f areas impacting sleep, 39 bipolar disorder. See also mood stabilizers deep brain stimulation, 186, 186f in children, 260 mapping mania symptoms onto circuits, 53 common comorbidities, 259f neuroimaging of activation in depression, 55f comorbid conditions and, 257 brain-derived neurotrophic factor (BDNF), 160 depressed phase of target gene for, 37 atypical antipsychotic agents in, 240f brain MAO-A, 127 bullet combos for, 264f brain stimulation, of depressed patients, 181 history, 19f brainstem lamotrigine as first-line treatment, 230 5HT3 receptor stimulation, and nausea or response to antidepressants, 20f vomiting, 79

Index 281

breast-feeding childbearing years, depression during, depression and treatment during, 164 167 children. See also autism lithium and, 260 “affective storms” in, 260 Buckeye bipolar bullets, 263, 264f antidepressants for, 67f bulimia, fluoxetine (Prozac) for, 81 bipolar disorder and mood stabilizers, 260 bupropion circuits metabolites, 101, 102f apathy, 41f potency for CYP450 2D6 inhibition, appetite, 46f 153 depressed mood, 40f with sertraline, 84 in depression, 37–44 buspirone, 199, 205 elevated/irritable mood, 49f and CYP 450 3A4, 156 fatigue, 43f mechanism of action augmentation, 201f, goal-directed activity, 53f 202f, 203f guilt, 47f malfunctioning caffeine and depression symptoms, 191 interactions with fluvoxamine, 152 for mania, 44–55 calcium channel blockers mania symptom, 50f L-type, 245, 246f mapping mania symptoms onto, 53 mechanism of action matching mania symptoms to, 48f on GABA, glutamate, sigma, and psychomotor symptoms, 45f dopamine, 224t sleep, 42f,51f VSSCs, synaptic vesicles, and carbonic suicide, 46f anhydrase, 223t weight, 46f putative clinical actions, 221t, 222t worthlessness, 47f California careful cocktail, 263, 264f citalopram, 86 California rocket fuel, 204f icon, 86f California sunshine, 265f, 266 potency for CYP450 2D6 inhibition, 153 carbamazepine (Equetro), 157, 226 clinical practice actions as mood stabilizer, 231f antidepressants in, 187 binding site of, 230f clomipramine (Anafranil), 145t, 153f and CYP 450 3A4, 156 inhibition of serotonin reuptake pump, icon, 228f 146 interaction with MAOIs, 143t clonidine, 169 for manic phase of bipolar disorder, clozapine, 107f 220 in combos for bipolar disorder, 261 mechanism of action Coaxil (tianeptine, Stablon), 145t on GABA, glutamate, sigma, and codeine dopamine, 224t and CYP450 2D6 inhibitors, 156 VSSCs, synaptic vesicles, and carbonic cognitive behavioral therapy (CBT), 187 anhydrase, 223t cognitive functioning putative clinical actions, 221t, 222t in depression, 100 and sedation, 157 “combos” (combination of medications) vs. valproate, 227 for bipolar disorder treatment, 261 and VSSCs, 255f COMT (catechol-O-methyl transferase), carbonic anhydrase, topiramate and, 235 24f cardiac arrhythmias and dopamine degradation, 92 from combining 3A4 substrates with and norepinephrine, 22 inhibitors, 157 concentration, 194 as tricyclic antidepressant side effect, and malfunctioning circuits, 193f 152f conduct disorder cerebrospinal fluid, 5HIAA in, 36 mania vs., 260, 261 “cheese reaction”, tyramine and, 133 constipation cheese, tyramine content of, 135f from NET inhibition, 95

282 Index

cortex. See also dorsolateral prefontal cortex bipolar vs. unipolar, treatment, 249 (DLPFC); orbitofrontal cortex; prefrontal chronic pain with cortex; ventromedial prefrontal cortex duloxetine for, 99 limbic, noradrenergic receptor stimulation in, comorbid psychiatric illness with, 195 95 disease progression in, 67 corticotrophin release factor 1 (CRF1) estrogen interaction with monoamines, antagonists, 211 169f cost-based selection of antidepressants, 190, 190f in females cyclobenzapine during childbearing years and pregnancy, interaction with MAOIs, 143t 164 cyclothymic temperament, 4, 7f during menopause, 168f, 171 with major depressive episodes, 11, 12f over life cycle, estrogen and, 162 cytochrome P450 (CYP450) enzyme systems during perimenopause, 167, 168f CYP450 1A2 substrates, 151, 153f during postpartum period, 167 inhibition, 153f SNRIs for, 171f inhibition consequences, 154f SSRIs for, 170f CYP450 2D6, 152 hypotheses for etiology, 36–37 inhibition, 87, 155f incidence across female life cycle, 163f inhibition consequences, 155f incidence across male life cycle, 164f paroxetine as substrate and inhibitor, 85 major, 3f,4 substrates, 154f antidepressant combinations as standard, and venlafaxine conversion, 96, 96f 199 CYP450 3A4, 156 common comorbidities, 198f combining inhibitors with substrates, 157 progressive nature of, 20f substrates and inhibitors, 156f relapse rates, 66f inducers, 157 remission rates, 65f pharmacokinetic actions, 151 symptom-based algorithm, 193f, 194f with mixed hypomania, 13 DBH (dopamine beta hydroxylase), 22 mixed states of mania and, 15t decongestants monoamine hypothesis, 68 and blood pressure, 141 normal monoamine neurotransmitter interaction with MAOIs, 142f activity, 35f interactions with drugs boosting reduced monoamine neurotransmitter sympathomimetic amines, 139 activity, 35f deep brain stimulation, 186, 186f monoamine receptor hypothesis, 36f delusions on mood chart, 2, 2f link to nucleus accumbens, 252f mood stabilizers for treating, 217f dementia. See also Alzheimer’s disease neuroimaging of brain activation in, 55f bipolarity in, 15, 15f neuronal response to sadness vs. happiness, demethylation, 153f 56f dendrites neurotransmitter receptor hypothesis, 36 spine formation, estrogen and trophic actions overlap with mania, 55 on, 160 risk across female life cycle, 163f Deplin (L-methylfolate), 177 symptoms, 37, 38f,44 for bipolar disorder, 247 matching to circuits, 39f depressed mood residual, 65f circuits, 40f treatment thyroid hormones and, 181f combination of medications, 200f depression MTHF vs. folic acid, 175 in bipolar disorder residual symptoms after, 191 history, 19f unipolar, distinguishing from bipolar response to antidepressants, 20f depression, 16, 17t, 18, 18f sleep disturbances in, 51f depression pharmacy, 187, 188f symptoms, 19f depressive temperament, 8f vs. unipolar depression, 16, 17t, 18, 18f Deprimyl (lofepramine, Gamanil), 145t

Index 283

desensitization reducing hyperactivity with lithium, 257f of somatodendritic 5HT1A autoreceptors, 74, release 75f serotonin regulation of, 25 desipramine (Norpramin, Pertofran), 145t, 153f dopamine agonists, for bipolar disorder, 266 inhibition of serotonin reuptake pump, 146 dopamine beta hydroxylase (DBH), 22 desmethylclomipramine, 153f “dopamine deficiency syndrome”, 94 desvenlafaxine, 97, 169 bupropion for, 104 icon, 97f dopamine transporter (DAT) venlafaxine conversion to, 96, 96f excessive occupancy, 102 desvenlafaxine XR (Pristiq), 89t sertaline for inhibiting, 83 dextromethorphan, 141, 266 dopaminergic combo, 200f interaction with MAOIs, 143, 143t dopaminergic neurons DHA (docosahexanoic acid), as mood stabilizer, MAO subtypes in, 125 246 dorsolateral prefrontal cortex (DLPFC) DHF (dihydrofolate), 175, 175f executive dysfunction localization in, 39 diabetes mellitus inefficient information processing, and neuropathy with, 98 distractibility, 52f diabolical learning, 21 dothiepin (Prothiaden), 145t Diagnostic and Statistical Manual of Mental double depression, 4, 5f Disorders (DSM), 193f doxepin (Sinequan, Adapin), 120, 145t bipolar spectrum, 9f dry mouth on depression symptoms, 38f from NET inhibition, 95 on mania symptoms, 48f “dual action” serotonin-norepinephrine agents, 92 diarrhea, for serotonin receptor stimulation, 79 duloxetine (Cymbalta, Xeristar), 89t, 98, 152, diet, tyramine modifications for MAO 154f inhibitors, 132t CYP450 2D6 impact on plasma levels, 155 dihydrofolate (DHF), 175, 175f as CYP450 2D6 inhibitor, 155f dihydrofolate reductase (DHFR), 175f icon, 98f dimerization, 159f interactions with fluvoxamine, 152 “dirty drugs”, 90, 90f potency for CYP450 2D6 inhibition, 153 disease progression, in depression, 67 dysphoric mania, 13 disinhibition, 160 dysthymia, 4, 4f distractibility, 54 on mood chart, 2, 2f distractibility circuit, 52f unremitting, 5f divalproex (Depakote), 222 dizziness, from paroxetine withdrawal, 85 eating disorders docosahexanoic acid (DHA), as mood SSRIs for, 70 stabilizer, 246 ECT (electroconvulsive therapy), 181 dopa, 22, 23f eicosapentanoic acid (EPA), as mood stabilizer, dopa decarboxylase (DDC), 22, 23f 246 dopamine, 1 Elavil (amitriptyline, Endep, Tryptizol, Loroxyl), 5HT2A receptors regulation of, 32f 120, 145t 5HT2A regulation of, 111 elderly 5HT2C receptors regulation of, 34f antidepressants for, 67, 67f antidepressants impact on synaptic depression action, 68 citalopram for, 87 antipsychotic agents and, 239, 240f electroconvulsive therapy (ECT), 181 depression from deficiency, 68f elevated mood circuits, 49f disinhibition, 126f emotion at sertonin 1A receptors, 119–122 depressed patient neuronal response, 56f dopa conversion to, 22, 23f enantiomers, for citalopram, 86 fluoxetine and release of, 82f,83f Endep (amitriptyline, Elavil, Tryptizol, Loroxyl), increase in prefrontal cortex, NET and, 92 120, 145t. See also nortriptyline (Pamelor, and mood disorders, 22 Endep, Aventyl) in prefrontal cortex, NET and, 93f endokinins, 212

284 Index

energy “fibrofog”, 100 loss fibromyalgia bupropion for, 104 desvenlafaxine for, 98 as SSRI side effect, 78 duloxetine for, 99 enthusiasm, loss gabapentin for, 236 bupropion for, 104 milnacipran for, 99 as SSRI side effect, 78 pregabalin for, 236 EPA (eicosapentanoic acid), as mood stabilizer, flibanserin (Ectris), 122 246 flight of ideas, 54 ephedrine, 141 fluoxetine (Prozac), 80–84, 152 with MAOIs, and hypertension, 141t and CYP 450 3A4, 156 ERT (estrogen replacement therapy), 167, 168, as CYP450 2D6 inhibitor, 155f 171 half-life of, 82 erythromycin, and CYP 450 3A4, 157 icon, 81f escitalopram, 87 impact on norepinephrine and dopamine icon, 89f release, 82f,83f eslicarbazepine, 229, 266 fluvastatin, 157 actions as mood stabilizer, 231f and CYP 450 3A4, 156 estradiol fluvoxamine, 85 activity-dependent spine formation by, 162f and CYP 450 3A4, 156 receptors for, 159f and CYP450 1A2 inhibition, 151, 153f estrogen, 158 icon, 86f as GABA inhibitor, 160 potency for CYP450 2D6 inhibition, 153 as glutamate activator, 160 folate, 175f interaction with monoamines deficiency and monoamines, 178f and depressed mood, 169f folic acid, 175f vasomotor symptoms from, 72f vs. MTHF, for depression, 175 and nuclear hormone receptors, 158, 159f folinic acid (Leucovorin), 174 regulation and major depression, over female life cycle, 162 GABA (gamma-aminobutyric acid) and trophic actions, on dendritic spine estrogen and, 158 formation, 160 topiramate and, 235 tropic properties, 161f valproate and, 222 estrogen receptors, 158 GABA (gamma-aminobutyric acid) estrogen replacement therapy (ERT), 167, 168, possible valproate sites of action, 226f 171 GABA (gamma-aminobutyric acid) inhibitor, estrogen response elements, 158, 159f estrogen as, 160 euthymia, on mood chart, 2, 2f GABA (gamma-aminobutyric acid) evidence-based selection of antidepressants, interneurons, estrogen and, 162f algorithm, 189, 189f GABA (gamma-aminobutyric acid) executive dysfunction, 44f neurons, 33f localization in dorsolateral prefrontal cortex, 39 gabapentin, 169, 235 executive functioning, 198 in combos for bipolar disorder, 263 extroversion, in hyperthymic temperament, 8f icon, 236f exuberance, in hyperthymic temperament, 8f mechanism of action on GABA, glutamate, sigma, and family history, and bipolar diagnosis, 17f dopamine, 224t fatigue VSSCs, synaptic vesicles, and carbonic circuits, 43f anhydrase, 223t link to prefrontal cortex, 39 putative clinical actions, 221t, 222t and malfunctioning circuits, 193f GAD (glutamic acid decarboxylase), 160 fetus gastrointestinal cramps, for serotonin receptor risks of antidepressants to, 166 stimulation, 79 risks of mood stabilizers and lithium to, 260 gastrointestinal upset, from paroxetine valproic acid toxicity, 225 withdrawal, 85

Index 285

genes histamine receptors 5HT2A antagonists and expression, 118 TCA antihistamine portion in, 150f hypothetic regulation of mood networks, 5-hydroxy-indole acetic acid (5HIAA), 31 54f in cerebrospinal fluid, 36 monoamine hypothesis of antidepressant hydroxylation, 154f action on expression, 71f hypersexuality, 252f in mood disorders, 55–57 hypersomnia, 198 gepirone, 199, 205 hypertension glucocorticoid antagonists, 211 agents combined with MAOIs causing, glutamate 141t 5HT2A antagonists and inhibitory action of hypertensive crisis, 130, 132, 134t HT1A on release, 119 reducing risk, 134 antipsychotic agents and, 239 hyperthermia, 143, 145 estrogen as activator, 160 hyperthermia/serotonin syndrome, from MAOIs mood stabilizers action on, 256f and other agents, 143t reducing hyperactivity, with atypical hyperthymic temperament, 8f,13 antipsychotics, 258f with depressive episode, 14f release hypomania, 2 lamotrigine impact on, 231 on antidepressant, 11 serotonin inhibition of, 124f mixed, depression with, 13 serotonin stimulation of, 123f on mood chart, 2, 2f topiramate and, 235 protracted or recurrent, 9 glutamic acid decarboxylase (GAD), 160 hypotension, MAO inhibitors and, 141 glycogen synthetase kinase 3 (GSK3), 218 hypothalamus glycogen synthetase kinase (GSK) 5HT3 receptor stimulation, and nausea or lithium and, 180 vomiting, 79 goal-directed activity inefficient information processing, and sleep circuit, 53f disturbances, 51f grandiosity, 54 and sleep disturbances, 39, 42f in hyperthymic temperament, 8f hypthalamic thermoregulatory centers, 168 inefficient information processing and, 50f imipramine (Tofranil), 145t, 153f GSK-3 (glycogen synthase kinase 3), 218 impulsivity guilt in hyperthymic temperament, 8f circuits, 47f information processing serotonin and, 41 in amygdala and depressed mood, 40f hair loss, as valproic acid side effect, 225 inefficient hallucinations in mania, 50f link to nucleus accumbens, 252f and sleep disturbances, 51f happiness inositol, for bipolar disorder, 247 depressed patient neuronal response, 56f in combos, 262 loss insomnia bupropion for, 104 and malfunctioning circuits, 193f as SSRI side effect, 78 trazodone for, 114 heroic combos treatment, 194 California rocket fuel, 204f, 205 insomnia/anxiety combo, 200f SNRI plus modafinil, 205, 205f interest, loss SNRI plus NDRI, 204f bupropion for, 104 SNRI plus stimulant, 204f as SSRI side effect, 78 SSRI plus NDRI, 200f interpersonal therapy (IPT), 187 hippocampus iproniazid, 122 neurons in, and BDNF, 37 IPT (interpersonal therapy), 187 histamine 1 receptors irritable mood circuits, 49f TCA blockade of, 147 isocarboxazid (Marplan), 123, 127t

286 Index

joy, loss li-do (lithium-Depakote/divalproex/valproate), bupropion for, 104 261, 262f as SSRI side effect, 78 licarbazepine, 229 binding site of, 230f ketamine mechanism of action for bipolar disorder, 243 on GABA, glutamate, sigma, and icon, 244f dopamine, 224t mechanism of action VSSCs, synaptic vesicles, and carbonic on GABA, glutamate, sigma, and anhydrase, 223t dopamine, 224t oxcarbazepine conversion to, 229f VSSCs, synaptic vesicles, and carbonic putative clinical actions, 221t, 222t anhydrase, 223t life cycle, antidepressants over, 67, 67f and NMDA receptor regulation, 256f limbic cortex, noradrenergic receptor stimulation possible actions in bipolar disorder, 246f in, 95 putative clinical actions, 221t, 222t lithium, 180, 216–220 site of action, 245f for bipolar disorder, 249 ketoconazole in combos and CYP 450 3A4, 157 for bipolar disorder, 261 for depression, 110f, 200f L channel, 245 for depression, 183f la-do (lamotrigine-Depakote), 262, 262f in bipolar disorder, 248 la-li-do (lamotrigine-lithium-Depakote), 262, for dopamine hyperactivity reduction, 257f 262f and fetal toxicity risk, 260 la-li (lamotrigine-lithium), 261, 262f mechanism of action, 218f Lami-quel, 263, 264f as mood stabilizer, 219f lamotrigine, 230–234 side effects of, 219 actions as mood stabilizer, 233f liver binding site of, 232f valproic acid toxicity, 225 for bipolar disorder, 249 lofepramine (Deprimyl, Gamanil), 145t with depression, 248 Loroxyl (amitriptyline, Elavil, Endep, Tryptizol), combination of medications with, 263, 120, 145t 264f lovastatin and glutamate reduction, 256f and CYP 450 3A4, 156 icon, 232f risk of muscle damage, 157 mechanism of action LuAA34893, 100, 100f on GABA, glutamate, sigma, and Ludiomil (maprotiline), 145t dopamine, 224t inhibition of serotonin reuptake pump, 146 VSSCs, synaptic vesicles, and carbonic anhydrase, 223t macrolide antibiotics, and CYP 450 3A4, 157 putative clinical actions, 221t, 222t major depressive disorder (MDD), 3f,4.See also rashes from, 231 depression sites of action, on glutamate release, 233f antidepressant combinations as standard, 199 and VSSCs, 255f common comorbidities, 198f Leucovorin (folinic acid), 174 progressive nature of, 20f levetiracetam, 237 relapse rates, 66f icon, 237f remission rates, 65f mechanism of action symptom-based algorithm, 193f, 194f on GABA, glutamate, sigma, and Manerix (moclobemide, Aurorix), 127t, 134 dopamine, 224t mania, 47f at SV2A symaptic vesicle sites, 238f on antidepressant, 11 VSSCs, synaptic vesicles, and carbonic cognitive symptoms, 52f anhydrase, 223t core symptoms of episode, 54 putative clinical actions, 221t, 222t mapping symptoms to circuits, 48f,53 levodopa, for Parkinson’s disease, MAO-B mixed states of depression and, 15t inhibition and, 127 on mood chart, 2, 2f

Index 287

mania, (Contd.) L-5-methyltetrahydrofolate (MTHF), 173, 175f, mood stabilizers for treating, 217f 176f neurotransmission instabililty and, 252 and antidepressants, 179f overlap with depression, 55 vs. folic acid, for depression, 175 patient response to no-go task, 57f and methylation reactions, 178 prepubertal and adolescent, 260 trimonoamine modulation of, 180f residual symptoms after first-line treatment, mianserin, 107f, 113 251 milnacipran (Ixel, Toledomin), 89t,99 sleep disturbances in, 51f icon, 99f symptoms and circuits, 44, 50f,55 mirtazapine, 107f, 109, 121 treatment actions at serotonin synapses, 112f with atypical antipsychotic agents, 237, actions overview, 114f 239f H1 antihistamine actions, 112, 113f with mood stabilizer, 216 icon, 111f maprotiline (Ludiomil), 145t SNRI plus, 204f inhibition of serotonin reuptake pump, 146 mixed hypomania, depression with, 13 Marplan (isocarboxazid), 123, 127t mixed mood state, 2 “medical food”, 177 moclobemide (Aurorix, Manerix), 127t, 134 melanocyte inhibitory factor (MIF-1), 211, combining with lamotrigine, 263, 264f 212f SNRI plus, 205f Mellaril (thioridazine) monoamine neurotransmitters, 1 and CYP450 2D6 inhibitors, 156 monoamine oxidase inhibitors (MAOIs), memantine 122–145 for bipolar disorder, 243 with amphetamine actions, 127t possible actions, 246f currently approved, 127t mechanism of action drug interactions, 139 on GABA, glutamate, sigma, and interaction with decongestants, 142f dopamine, 224t interaction with SRIs, 144f VSSCs, synaptic vesicles, and carbonic irreversible, dangerous tyramine levels with, anhydrase, 223t 140f and NMDA receptor regulation, 256f new developments, 133 putative clinical actions, 221t, 222t tyramine dietary modifications for, 132t memory monoamine oxidase (MAO) loss enzymes, 127t electroconvulsive therapy and, 182 and norepinephrine, 22, 24f men, depression incidence across life subtype A inhibition, 128f cycle, 164f combined with subtype B inhibition, 131f menopause, depression and treatment during, and dietary tyramine management, 130 168f, 171 and tyramine, 134f menstrual cycle, reproductive hormones and subtype A, norepinephrine destruction by, 132f synaptogenesis, 161f subtype B inhibition, 129f “menstrual magnification”, 164 transdermal delivery, 136–139 meperidine, interaction with MAOIs, 143, 143t subtypes, 125 methadone monoamine transporters, 108 interaction with MAOIs, 143, 143t monoamines 6-(S)-5-methyl-tetrahydrofolate (MTHF), 247 estrogen interaction with, and depressed methylation, MTHF regulation of, 178 mood, 169f methylene tetrahydrofolate reductase (THF-R), folate deficiency and, 178f 175f interaction with estrogen, vasomotor L-methylfolate (Deplin), 177 symptoms from, 72f for bipolar disorder, 247 monohydroxyderivative, 229 in combos, 262 mood chart, 2f methylphenidate mood disorders and blood pressure, 141 description, 2 with MAOIs, and hypertension, 141t future treatments for, 207–213

288 Index

genes and neuroimaging in, 55–57 nefazodone, 120, 187 mapping, 2f and CYP 450 3A4, 156 neurotransmitters and circuits in, 22–28 icon, 115f prevalence of, 16f negative affect, 47f progressive nature of, 18 increased, 43 treatment-resistant, 21 vs. reduced positive affect, 191 mood episodes, 3f negative feedback regulatory signal, mood networks, genes hypothetically regulating, 24 54f nemifitide, 211, 212f mood stabilizers, 216. See also lithium neuroimaging anticonvulsants, 220. See also specific agents in depression, 55f atypical antipsychotic agents, 237, in mood disorders, 55–57 242f neurokinin antagonists, 212 in clinical practice, 248–266 neurokinin receptors, 213t pharmacy, 248, 249f neurokinins residual symptoms after first-line treatment, targeting with antidepressants in 250–258 development, 208t selection process, 248 neurons symptom-based algorithm for sequential cyclical activation, estrogen and, 160 treatment, 248 noradrenergic, 22–24 combinations for bipolar disorder, 261 neurotransmission. See also chemical definition, 216 neurotransmission and fetal toxicity risk, 260 unstable and excessive in bipolar disorder, future options, 266 254f gender differences, 260 neurotransmitter receptor hypothesis of and glutamate, 256f depression, 36 mechanism of action neurotransmitters on GABA, glutamate, sigma, and changes in receptor sensitivity, 69 dopamine, 224t in depression treatment, 200f VSSCs, synaptic vesicles, and carbonic receptor hypothesis of antidepressant action, anhydrase, 223t 70f putative clinical actions, 221t, 222t nitric oxide synthetase, inhibiting, 85 symptom-based algorithm NK1 antagonists (substance P antagonists), deconstructing mania/bipolar spectrum 213 disorder symptoms, 251f NK3 antagonists, 213 deconstructing mania diagnostic symptoms, NMDA (N-methyl-d-aspartate) 250f receptors symptom matching to circuits, 252f blocking glutamate actions at, 256f targeting neurotransmitters, 253f ketamine binding to, 245f for treating depression, 217f noradrenergic and specific serotonergic for treating mania, 217f antidepressant (NaSSA), mirtazapine and VSSCs, 255f as, 111f muscarinic cholinergic receptors, 95 noradrenergic neurons, 22–24 TCA blockade of, 147 MAO subtypes in, 125 myoclonus, from SSRIs, 79 norepinephrine and dopamine reuptake inhibitors (NDRIs), 100–104 naltrexone action, 101f in combos for bipolar disorder, 263 actions in prefrontal cortex and striatum, Nardil (phenelzine), 123, 127t 103f nausea icon, 101f from 5HT3 receptor stimulation, 79 SNRI plus, 204f from venlafaxine, 97 “norepinephrine deficiency syndrome”, 94 NDDIs (norepinephrine dopamine norepinephrine dopamine disinhibitors disinhibitors), 206 (NDDIs), 206 NE reuptake pump, 22 mirtazapine as, 111

Index 289

norepinephrine (NE), 1. See also serotonin nuclear hormone receptors norepinephrine reuptake inhibitors and estrogen, 158, 159f (SNRIs) nuclear ligand–activated transcription factors, 5HT2A receptors regulation of, 32f 158, 159f and alpha 2 antagonists, 108f nucleus accumbens antidepressants impact on synaptic action, 68 5HT2C receptors regulation of dopamine, 34f antipsychotic agents and, 239, 240f and delusions and hallucinations, 252f autoreceptors as gatekeepers, 26f depression from deficiency, 68f obsessive compulsive disorder and depression symptoms, 94 fluvoxamine for, 85, 86 disinhibition, 110f, 126f olanzapine at sertonin 1A receptors, 119–122 actions as mood stabilizer, 241f fluoxetine and release of, 82f,83f in combos for bipolar disorder, 261 and mood disorders, 22 fluoxetine with, 81 normal destruction by MAO-A, 132f pharmacological actions, 241f regulation of seretonin release, 24, 28, 28f omega-3 fatty acids as accelerator, 30f for bipolar disorder, 246 bidirectional control, 31f in combos for bipolar disorder, 262 as brake, 29f opiates release interaction with MAOIs, 143, 143t presynaptic alpha 2 receptor regulation, 23 oppositional defiant disorder serotonin regulation of, 25 optimism, in hyperthymic temperament, 8f tyramine and, 133f orbitofrontal cortex synthesis, 22, 23f manic episode symptoms linked to, 54 termination of action, 22, 24f risk taking and, 50f transport pump, 22 overconfidence, in hyperthymic temperament, 8f tricyclic antidepressant to block reuptake oxcarbazepine, 229 pump, 146 actions as mood stabilizer, 231f turning off its own release, 106 binding site of, 230f norepinephrine receptors, 25f converion to licarbazepine, 229f norepinephrine reuptake inhibition (NRI), 91f mechanism of action norepinephrine reuptake pump, 92 on GABA, glutamate, sigma, and norepinephrine selective reuptake inhibitors dopamine, 224t (NRIs) VSSCs, synaptic vesicles, and carbonic actions, 106f anhydrase, 223t icon, 105f putative clinical actions, 221t, 222t plus mirtazapine, 204f and VSSCs, 255f plus modafinil, 205f plus NDRI, 204f pain. See also chronic pain; fibromyalgia plus stimulant, 204f in depression, 198 norepinephrine transporter (NET), 22, 24f gabapentin for, 235 inhibition, 105 pregabalin for, 235 and dopamine in prefrontal cortex, 92, 93f paliperidone, 107f high degrees of, and sedation, 106 actions as mood stabilizer, 241f potential side effects, 94 in combos for bipolar disorder, 261 therapeutic actions of, 94 pharmacological actions, 241f norquetiapine pancreas, valproic acid toxicity, 225 actions as mood stabilizer, 241f panic disorder pharmacological actions, 241f in children, 261 nortriptyline, 120 MAO inhibitors for, 123 nortriptyline (Pamelor, Endep, Aventyl), 145t parkinsonism inhibition of serotonin reuptake pump, 146 from SSRIs, 78 with interpersonal psychotherapy, 187 Parkinson’s disease, 186 “not otherwise specified” (NOS), 9 levodopa for, MAO-B inhibition and, 127 novel peptides, 212f protoxins and, 130

290 Index

paroxetine, 84, 152, 154f fatigue and, 39 CYP450 2D6 impact on plasma levels, 155 impact on suicidal ideation, 41 as CYP450 2D6 inhibitor, 155f NDRI actions in, 103f icon, 85f regulatory importance of dopamine, 92 peptides and sleep disturbances, 39, 42f novel, 212f pregabalin, 235 perimenopause in combos for bipolar disorder, 263 depression and treatment during, 167, 168f icon, 236f depression risk during, 163f mechanism of action desvenlafaxine for reducing symptoms, 98 on GABA, glutamate, sigma, and perospirone, 107f dopamine, 224t phencyclidine (PCP), 244 VSSCs, synaptic vesicles, and carbonic phenelzine (Nardil), 123, 127t anhydrase, 223t phenethylamine, 125 putative clinical actions, 221t, 222t phentermine, with MAOIs, and hypertension, pregnancy 141t antidepressant risks or avoidance during, phenylephrine, 140 166t with MAOIs, and hypertension, 141t and bipolar mood episodes, 259 phenylpropanolamine, 141 depression during, 164 with MAOIs, and hypertension, 141t estrogen levels during, 165 pimozide (Orap) premenstrual dysphoric disorder (PMDD), 164 combining 3A4 inhibitor with, 157 SSRIs for, 70 and CYP 450 3A4, 156 premenstrual phase, bipolar disorder during, pindolol, 199 259 pizza, tyramine content of commercial-chain, premenstrual syndrome (PMS), 164 136f presynaptic axon terminals, 72 placebo, 62 progesterone, 160 response rates, 63f L-prolyl-L-leucy-L-glycinamide (PLG), 211, substitution, 64f 212f pleasure propoxyphene, interaction with MAOIs, 143, loss 143t bupropion for, 104 protease inhibitors as SSRI side effect, 78 and CYP 450 3A4, 157 PLG (L-prolyl-L-leucy-L-glycinamide), 211 Prothiaden (dothiepin), 145t PMDD (premenstrual dysphoric disorder), 164 protoxins, and Parkinson’s disease, 130 SSRIs for, 70 protriptyline (Vivactil), 145t PMS (premenstrual syndrome), 164 inhibition of serotonin reuptake pump, 146 positive affect, 47f ”pseudo anticholinergic” syndrome, 95 reduced, 43 pseudoephedrine, 141 vs. increased negative affect, 191 with MAOIs, and hypertension, 141t postpartum period psychomotor retardation and bipolar mood episodes, 259 from SSRIs, 78 depression and treatment during, 167 psychomotor symptoms depression risk during, 163f, 165 circuits, 45f postpartum psychosis, 167 in depression, 39 postsynaptic receptors psychosis and norepinephrine, 23 postpartum, 167 postsynaptic serotonin receptors, excessive psychotherapy, 187 stimulation of, 145 pramipexole, 266 Quel kit, 263, 264f pravastatin, 157 quetiapine, 107f and CYP 450 3A4, 156 actions as mood stabilizer, 241f prefrontal cortex, 252f in combos for bipolar disorder, 263, 264f dopamine increase from NET inhibition, 92, pharmacological actions, 241f 93f quinidine, 266

Index 291

R enantiomer in combos for bipolar disorder, 261 for citalopram, 86 pharmacological actions, 241f at serotonin transporter, 88f ropinirole, 266 racemic citalopram, 86 racing thoughts, 54 S-adenosyl-methionine (SAMs), 178 inefficient information processing and, in combos for bipolar disorder, 262 50f trimonoamine modulation of, 180f radafaxine, 102, 104f S enantiomer rapid cycling, 2, 4, 6f for citalopram, 86 switches, 6f in escitalopram, 87 rapid “poop out”, 10f at serotonin transporter, 88f rasaligine (Agilect/Azilect), 127t sad temperament, 8f for Parkinson’s disease, 130 sadness, depressed patient neuronal response, rashes 56f from lamotrigine, 231 saredutant, 213 from zonisamide, 235 schizoaffective disorder, 9, 10f reboxetine, 105 sedation and CYP 450 3A4, 156 NET inhibition and, 106 potency for CYP450 2D6 inhibition, as valproic acid side effect, 225 153 selegiline, 124, 127t recovery, 61f for Parkinson’s disease, 130 recurrence of depression, 61f transdermal delivery system for, 135, 136, relapse, 64 139f of depression, 61f MAO inhibitors, 139 frequency with drug continuation, 63f self-confidence, loss rates in major depressive disorders, 66f bupropion for, 104 remission as SSRI side effect, 78 antidepressant combinations for, 199 self-esteem, 54 rates for SNRIs vs. SSRIs, 91 SEP 227, 229, 104f rates in major depressive disorders, 65f Sequenced Treatment Alternatives to Relieve of symptoms, 61f Depression (STAR-D) trial, 64 as treatment goal, 60 serine hydroxyl methyl transferase (SHMT), reproductive hormones, across menstrual cycle, 175f 161f serotonin 1A combo, for depression, 200f residual symptoms, in depression, 65f serotonin 2A combo, 200f response, to depression treatment, 60, 60f serotonin (5HT), 1 restlessness, from paroxetine withdrawal, 85 5HT1A agonist, mirtazapine action, 109 reversible inhibitor of MAO-A (RIMA), 135, 5HT1A receptors 138f SARIs action at, 118f riluzole, 234 5HT2A antagonists and glutamate reduction, 256f and inhibitory action of serotonin 1A on icon, 234f glutamate release, 119 mechanism of action 5HT2A receptors on GABA, glutamate, sigma, and blockade at, 122f dopamine, 224t and gene expression from 5HT1A receptors, VSSCs, synaptic vesicles, and carbonic 121f anhydrase, 223t NE and DA disinhibition at HT1A possible actions in bipolar disorder, 246f receptors, 119–122 putative clinical actions, 221t, 222t regulation of NE and DA release, 32f sites of action, on glutamate release, 233f SARIs action at, 117, 117f RIMA (reversible inhibitor of MAO-A), 135, 5HT2C antagonist, mirtazapine action, 111 138f 5HT2C receptors, 207 risk taking, orbital frontal cortex and, 50f fluoxetine blockade of, 82f risperidone, 107f NE and DA disinhibition at HT1A actions as mood stabilizer, 241f receptors, 119–122

292 Index

regulation of dopamine in nucleus serotonin norepinephrine reuptake inhibitors accumbens, 34f (SNRIs), 89 regulation of NE and DA release, 33f actions, 91f serotonin action, 80 bicifidine, 100, 100f 5HT3 antagonists, 111 for depressed women with fluctuating 5HT3 receptors estrogen, 171f stimulation of, 79 desvenlafaxine, 97 and alpha 2 antagonists, 108f icon, 97f antagonists synergy with SERT inhibition, duloxetine (Cymbalta, Xeristar), 98 116–122 icon, 98f antidepressants impact on synaptic action, 68 icon, 89f, 100f antipsychotic agents and, 239, 240f listing, 89t depression from deficiency, 68f LuAA34893, 100, 100f disinhibition, 110f milnacipran (Ixel, Toledomin), 99 genes, expression stimulation through 5HT1A icon, 99f receptors, 120f potential side effects of NET inhibition, 94 glutamate release stimulation, 123f remission rates compared with SSRIs, 91 increasing release after alpha 2 antagonist, serotonergic, noradrenergic and dopaminergic 107 pathways and, 92–95 mirtazapine actions at synapses, 112f sibutramine, 100, 100f and mood disorders, 22 for vasomotor symptom treatment, 174f norepinephrine regulation of, 28, 28f venlafaxine XR (Effexor XR; Efexor XR), as accelerator, 30f 95–97 bidirectional control, 31f conversion to desvenlafaxine, 96, 96f as brake, 29f icon, 96f novel targets, 207 serotonin receptors regulation of NE and DA release, 25 postsynaptic release excessive stimulation of, 145 norepinephrine regulation of, 24 serotonin reuptake inhibitor (SRI), 91f tricyclic antidepressant to block reuptake interaction with MAOIs, 143, 144f pump, 146 serotonin selective reuptake inhibitors (SSRIs), serotonin antagonist/reuptake inhibitors 70, 72f, 87, 189f (SARIs), 113, 115f, 122 action potential, 72f actions at serotonin synapses, 115f citalopram, 86 mechanism of action icon, 86f 5HT2A antagonism and inhibitory action at common features, 72 5HT1A, 125f for depressed women with fluctuating baseline postsynaptic actions, 116f estrogen, 170f disinhibition of norepinephrine and escitalopram, 87 dopamine, 126f icon, 89f gene expression, 121f, 122f and estrogen impact, 172 glutamate release inhibition, 124f fluoxetine (Prozac), 80–84. See also fluoxetine glutamate release stimulation, 123f (Prozac) serotonin excitatory at 5HT2A receptors, fluvoxamine, 85 117f icon, 86f serotonin inhibitory at 5HT1A receptors, listing, 71t 118f mechanism of action, 73f,74f,75f,76f, synergy between 5HT1A and 5HT2A, 119f 77f serotonin deficiency syndrome, 78 paroxetine, 84 serotonin neuron, somatodendritic area of, 74, icon, 85f 75f patient response to different, 80 serotonin norepinephrine disinhibitors (SNDIs), pharmacological and molecular mechanism of 106 action, 72–76 serotonin-norepinephrine-dopamine-reuptake remission rates compared with SNRIs, 91 inhibitors (SNDRIs), 209 secondary pharmacological properties, 79f

Index 293

serotonin selective reuptake inhibitors (SSRIs), Stablon (tianeptine, Coaxil), 145t (Contd.) STAR-D (Sequenced Treatment Alternatives to serotonin pathways and receptors that Relieve Depression) trial, 64 hypothetically mediate actions, 77–79 Stevens-Johnson syndrome, 231, 235 sertraline, 83 stimulants icon, 84f and blood pressure, 141 side effects of, 78 SNRI plus, 204f tolerance to side effects, 75 striatal complex for vasomotor symptom treatment, 173f striatum, 252f serotonin syndrome, 143 NDRI actions in, 103f serotonin transporter (SERT), 143 substance abuse, 252f. See also specific substance inhibition of, 72 types R vs. S enantiomer at, 88f bipolar disorder associated with, 11 SSRI block of, 77f topiramate and, 235 sertraline, 83 “substance-induced mood disorder”, 11 and CYP 450 3A4, 156 substance P antagonists, 213 icon, 84f suicidal ideation, 41 potency for CYP450 2D6 inhibition, 153 in young adults, from antidepressants, 68 setiptilene, 113 suicidality sexual dysfunction, 85, 199 circuits, 46f mirtazapine to avoid, 110 in female adolescents, from antidepressants, from SSRIs, 79 165 SHMT (serine hydroxyl methyl transferase), 175f unrecognized bipolar disorder and, 16 sibutramine, 100, 100f “suicide inhibitor”, 124 interaction with MAOIs, 143t suicide, risk in depressed mothers, 166 with MAOIs, and hypertension, 141t Surmontil (trimipramine), 145t sigma-1 receptor binding sympathetic nervous system of fluvoxamine, 85 noradrenergic receptor stimulation in, 95 of sertaline, 83 sympathomimetic amines, decongestant sigma 1 site, 266 interaction with drugs boosting, 139 ”sigma enigma”, 85 symptom-based selection of antidepressants, 191, signal transduction cascades 192f valproate and, 222, 227f algorithm for, 193f, 194f, 195f, 196f, 197f simvastatin synaptic vesicles and CYP 450 3A4, 156 levetiracetam mechanism of action at SV2A risk of muscle damage, 157 sites, 238f sleep circuits, 42f,51f T3, in combos for bipolar disorder, 262 trazodone to improve, 114 tachykinins, 212, 212t sleep disturbances, 54 temperament, 4 brain areas impacting, 39 depressive, 8f gabapentin for, 236 hyperthymic, 8f,13 pregabalin for, 236 with depressive episode, 14f sleepiness/hypersomnia in daytime, 198 Tennessee mood shine, 263, 264f in depression, 197 tetrahydrobiopterin (BH4), 173 smoking. See also nicotine cofactor for trimonoamine neurotransmitter as CYP450 inducer, 157 synthesis, 177f SNDRIs (serotonin-norepinephrine-dopamine- MTHF regulation of, 176f reuptake inhibitors), tetrahydrofolate (THF), 175f 209 thalamus social anxiety disorder inefficient information processing, and sleep fluvoxamine for, 86 disturbances, 51f social phobia, MAO inhibitors for, 123 and sleep disturbances, 39, 42f social stigma, of electroconvulsive therapy, 182 theophyllin, interactions with fluvoxamine, 152 somatodendritic alpha 2 receptors, 23, 27f theophylline, 154f

294 Index

thermoregulation, disruption in, 145 side effects THF-R (methylene tetrahydrofolate reductase), coma, seizures, arrhythmia, death, 152f 175f constipation, blurred vision, dry mouth, and THF (tetrahydrofolate), 175f drowsiness, 150f thioridazine (Mellaril) dizziness, drowsiness, decreased blood and CYP450 2D6 inhibitors, 156 pressure, 151f thyroid weight gain and drowsiness, 150f dysfunction, men vs. women, 259 therapeutic actions of thyroid hormones, 179 5HT2A receptor block, 149f as augmenting agent, 182f 5HT2C receptor block, 149f for bipolar disorder, 247 norepinephrine reuptake inhibition (NRI), in combination treatments for depression, 148f 200f serotonin reuptake inhibitor (SRI), 148f and depressed mood, 181f trimipramine (Surmontil), 145t tianeptine (Coaxil, Stablon), 145t trimonoamine neurotransmitter synthesis, tingling, from paroxetine withdrawal, 85 tetrahydrobiopterin (BH4) cofactor for, TMMs (trimonoaminergic modulators), 177f 157–187 trimonoaminergic modulators (TMMs), 157–187 estrogen as, 158 estrogen as, 158 L-5-methyltetrahydrofolate (MTHF) as, L-5-methyltetrahydrofolate (MTHF) as, 173 173 trimonoaminergic neurotransmitter system, 1, TMS (transcranial magnetic stimulation), 185, 22 185f antipsychotic agents and, 239 Toledomin (milnacipran, Ixel), 89t, dysregulation of, 168 99 triple reuptake inhibitors (TRIs), 206, 209 topiramate, 234, 257 icon, 209f in combos for bipolar disorder, 263 trophic actions, and estrogen, on dendritic spine icon, 235 formation, 160 mechanism of action Tryptizol (amitriptyline, Elavil, Endep, Loroxyl), on GABA, glutamate, sigma, and 120, 145t dopamine, 224t tryptophan hydroxylase (TRY-OH), 173 VSSCs, synaptic vesicles, and carbonic tyramine anhydrase, 223t and blood pressure, 137 putative clinical actions, 221t, 222t cheese content, 135f and VSSCs, 255f dangerous levels with irreversible MAO-A toxic epidermal necrolysis, 231, 235 inhibitors, 140f tramadol, interaction with MAOIs, 143, 143t MAO-A inhibitor and, 138f transcranial magnetic stimulation (TMS), 185, MAO-A inhibition and, 134f 185f and norepinephrine release, 133f tranylcypromine (Parnate), 123, 124, 127t pizza chain content of, 136f trazodone, 113 reactions and dietary restrictions, 130, 132t 5HT2A inhibition by, 117 wine content, 137f icon, 115f tyrosine for insomnia, 114 norepinephrine synthesis from, 22, 23f treatment-resistant mood disorders, 21 tyrosine hydroxylase (TOH), 22, 23f, 173 triazolam and CYP 450 3A4, 156 unipolar depression, 2 and sedation, 157 distinguishing from bipolar depression, 16, tricyclic antidepressants (TCAs), 90, 145–151 17t, 18, 18f archaic terminology, 150 impact of chronic and widespread chemical structure, 146f undertreatment, 21 development, 145 misdiagnosis, 16 icons, 147f unstable form of, 9 listing of those still in use, 145t urinary hesitancy, from milnacipran, 100 major limitation, 146 urinary retention, from NET inhibition, 95

Index 295

vagus nerve stimulation (VNS), 182, 184f vomiting valproate from 5HT3 receptor stimulation, 79 actions as mood stabilizer, 228f for bipolar disorder, 249 “Walt Disney”, 265f, 266 vs. carbamazepine, 227 weight in combos for bipolar disorder, 261 changes in, 41 GABA and, 222 circuits, 46f for manic phase of bipolar disorder, 220 weight gain mechanism of action from 5HT2C antagonists and/or mirtazapine, on GABA, glutamate, sigma, and 111 dopamine, 224t from mirtazapine, 112 VSSCs, synaptic vesicles, and carbonic as valproic acid side effect, 225 anhydrase, 223t weight loss possible sites of action on GABA, 226f topiramate and, 235 possible sites of action on VSSCs, 225f “Well-oft” (Wellbutrin with Zoloft), 84 putative clinical actions, 221t, 222t wine, tyramine content, 137f and VSSCs, 255f women valproic acid, 220 bipolar disorder and, 258 icon, 224t depression incidence across, 163f side effects, 225 depression risk across, 163f varenicline estrogen and/or antidepressant use across, in combos for bipolar disorder, 263 165f vasomotor symptoms, 168 estrogen regulation and major depression from estrogen interaction with monoamines, over, 162 72f suicidality in adolescents, from antidepressants, link to depression, 198 165 in perimenopause, 167 thyroid dysfunction, 259 treatment, 169 worthlessness with desvenlafaxine, 98 circuits, 47f with SNRIs, 174f serotonin and, 41 with SSRIs, 173f vasopressin 1B antagonists, 211 YM992, 121 venlafaxine XR (Effexor XR; Efexor XR), 89t, yohimbine, 113 91, 95–97, 152, 154f conversion to desvenlafaxine, 96, 96f zipa-do, 265f, 266 CYP450 2D6 impact on plasma levels, 155 zipa-la, 265f, 266 icon, 96f zipa-li, 265f, 266 ventromedial prefrontal cortex (VMPFC) zipa-li-do-la, 265f, 266 emotional symptom regulation by, 56f ziprasidone manic episode symptoms linked to, 54 actions as mood stabilizer, 241f vesicles, 22 in combos for bipolar disorder, 261, 265f, vesicular monoamine transporters (VMATs), 22, 266 23f pharmacological actions, 241f Vivactil (protriptyline), 145t zonisamide, 235, 257 inhibition of serotonin reuptake pump, 146 in combos for bipolar disorder, 263 VNS (vagus nerve stimulation), 182, 184f icon, 236f voltage-sensitive calcium channels (VSCCs) mechanism of action TCA blockade of, 147 on GABA, glutamate, sigma, and voltage-sensitive sodium channels (VSSCs) dopamine, 224t carbamazepine acton on, 226 VSSCs, synaptic vesicles, and carbonic mood stabilizers action on, 255f anhydrase, 223t oxcarbazepine and, 229 putative clinical actions, 221t, 222t valproate and, 220 and VSSCs, 255f

296 Index