NE terminal Norepinephrine (NE) receptor (b 1 , b 2 , a 1 etc.) Serotonin receptor (5-HT 1A , 5-HT 2 etc.) Blocks presynaptic a 2 -adreno- ceptors Trazodone is a weak inhibitor of 5-HT reuptake 5-HT terminal Blocks postsynaptic 5-HT 2 receptors Figure 9.31 The mode of action of trazodone.Trazodone is a weak inhibitor of serotonin reuptake and can increase norepinephrine release as a result of its antagonistic action on presynaptic a 2 -adrenoceptors. It also blocks postsynaptic 5-HT 2 receptors Trazodone Maprotiline Tryptophan Bupropion N N Cl Cl N O N(CH 2 ) 3 N (CH 2 ) 3 NHMe H COOH CH 2 CH NHC(CH 3 ) 3 NH 2 N COCHCH 3 Figure 9.30 Molecular structures of trazodone, maprotiline, L-tryptophan and bupropion ©2002 CRC Press LLC Sedation Drowsiness Anxiety (in high doses) Nausea Orthostatic hypotension Priapism Figure 9.32 Side-effects of trazodone NE terminal Norepinephrine (NE) receptor (b 1 , b 2 , a 1 etc.) Serotonin receptor (5-HT 1A , 5-HT 2 etc.) Maprotiline acts at uptake site Maprotiline acts at uptake site 5-HT terminal Figure 9.33 The mode of action of maprotiline. Maprotiline is a modified tricyclic antidepresssant (TCA) that has similar efficacy to the TCAs ©2002 CRC Press LLC NE terminal Norepinephrine (NE) receptor (b 1 , a 1 etc.) or a 1 -receptor on serotonergic cell body or a 2 - heteroceptor on serotonergic nerve terminal Serotonin receptor 5-HT terminal Mianserin blocks a 2 - autoreceptor Desensitization of 5-HT 1B /5-HT 1D receptors Increased activity of 5-HT 1A receptors 5-HT 2 and 5-HT 3 receptors blocked a 2 -heteroceptor on serotonergic nerve terminal stimulates increased release of serotonin Figure 9.36 The mode of action of mianserin. Mianserin, like mirtazapine, enhances noradrenergic and serotonergic function by block- ing the inhibitory a 2 -adrenoceptors on noradrenergic terminals and the a 2 -heteroceptors on serotonergic terminals. However, mir- tazapine is more effective than mianserin in enhancing serotonergic function, as it increases the firing rate of serotonergic neurons. Mianserin is less potent in blocking postsynaptic serotonin receptors * But to a lesser extent than older TCAs Rashes Possible weight gain Blurred vision* Glaucoma* Cardiotoxicity Tachycardia* Orthostatic hypotension* Urinary retention* Constipation Dry mouth* Confusion* Sedation* Dizziness* Reduced sexual funct ion* N N CH 3 Figure 9.34 The side-effects of maprotiline Figure 9.35 Molecular structure of mianserin ©2002 CRC Press LLC Drowsiness Dizziness Sedation Weight gain Lowering of white blood cell count (rare) Agranulocytosis (rare) Orthostatic hypotension Hepatitis (very rare) Arthritis (very rare) Dyspepsia Nausea Figure 9.37 The side-effects of mianserin Sedation Headache Nausea Myoclonus Eosinophilia–myalgia syndrome * Figure 9.38 The side-effects of L-tryptophan. *, Eosinophilia– myalgia syndrome was linked to contamination of some trypto- phan-containing products during the manufacturing process, therefore close monitoring is required Insomnia Headache Seizures Nausea Vomiting Dry mouth Taste disorders Fever Rashes Figure 9.39 The side-effects of bupropion ©2002 CRC Press LLC Drugs used for treatment of generalized anxiety disorder Benzodiazepines Partial 5-HT receptor agonist (buspirone) Some tricyclic antidepressants Paroxetine Trazodone Venlafaxine Trifluoperazine Proven efficacy from randomized control trials Causes troublesome sedation and long-term risk of dependance – best used when anxiety symptoms are particularly distressing or disabl i Antipsychotic sometimes used – effec t in reducing anxiety, but associated w a number of long-term side-effects Discuss need for long-term treatment Establish degree of affective morbidity Aim for lithium level of 0.5–1.0 mmol/l Use a starting dose of approximately 600 mg in otherwise healthy young adults Weigh the patient Perform pregnancy test in women of child-bearing poten t Perform blood tests for renal and thyroid function Determine lithium level after 5–7 days Figure 9.41 Lithium treatment plan. Lithium should only be used in bipolar prophylaxis when it is reasonable to anticipate treatment lasting more than 2 years. Shorter periods of treatment are associated with an increased risk of rebound mania on stopping lithium Figure 9.40 Drug treatment of generalized anxiety disorder ©2002 CRC Press LLC 1.5 1.0 0.4 0 Serum lithium (mmol/l) Confusion Slurred speech, ataxia Coarse tremor, vomiting, diarrhea Death Side-effects Polyuria Tremor of hands Metallic taste Reversible nephrogenic diabetes insipidus Weight gain Hypothyroidism Toxic doses Therapeutic doses Toxic effects Figure 9.42 The side-effects of lithium and its spectrum of action. Graph reproduced with permission from Stevens L, Rodn I. Psychiatry: an Illustrated Colour Text. Edinburgh: Churchill Livingstone, 2001:25 N CONH 2 Figure 9.43 Example of an anticonvulsant drug (carbamazepine). Carbemazepine has the tricyclic structure of many older antide- pressants and conventional antipsychotic drugs Side-effects Weight gain Teratogenic effects on fetuses Impaired attention Impaired memory Thirst Leukocytosis Polyuria Impaired renal tubular function Skin problems Tremor Toxic effects Drowsiness Disorientation Dysarthria Convulsion Coma Pulmonary complications Cardiac complications Nausea and vomiting Tremor Hypothyroidism Non-toxic goiter Headache Drowsiness Nausea and vomiting Hepatic problems Skin rashes Blood dyscrasias Teratogenic effects Figure 9.44 The general side-effects of anticonvulsants. However, drugs differ in their relative propensity to cause par- ticular adverse effects.Always refer to the prescribers informa- tion ©2002 CRC Press LLC Sudden or unexpected death Miscarriage, death of baby, child or sibling Multiple prior bereavements A history of mental illness (e.g. depression or anxiety) Death of cohabiting part- ner, same-sex partner, etc. (may result in disen- franchized grief) Ambivalence of dependent relationships with the person who has been lost Death occurred as a result of a disease with a potential stigma (e.g. AIDS) Death resulted from accident in which bereaved was involved/responsible Death occurred due to murder or where legal proceedings involved Death following which a postmortem and/or inquest is required Risk factors associated with poor outcome in bereavement Figure 11.2 Risk factors associated with bereavement Figure 10.1 Light therapy for treatment of depression.Photograph courtesy of SAD Lightbox Co.Ltd.,High Wycombe, UK Figure 10.2 Transcranial magnetic stimulation is stil an experi- mental approach to the treatment of depression. It appears to show efficacy in acute treatment and may have value in continu- ation treatment Figure 11.1 The techniques of cognitive–behavior therapy Keeping a daily record of activities and negative thoughts Monitoring negative thoughts associated with worsening mood Challenging negative thoughts Using imagination to ‘replay’ events Questioning the assumptions that lead to negative thoughts Planning rewarding activities throughout the day Praising oneself for achievements Dividing complex tasks into achievable components Anticipating performance in challenging situations ©2002 CRC Press LLC . receptor 5-HT terminal Mianserin blocks a 2 - autoreceptor Desensitization of 5-HT 1B /5-HT 1D receptors Increased activity of 5-HT 1A receptors 5-HT 2 and 5-HT 3 receptors blocked a 2 -heteroceptor on. 2001:25 N CONH 2 Figure 9.43 Example of an anticonvulsant drug (carbamazepine). Carbemazepine has the tricyclic structure of many older antide- pressants and conventional antipsychotic drugs Side-effects Weight gain Teratogenic. death Miscarriage, death of baby, child or sibling Multiple prior bereavements A history of mental illness (e.g. depression or anxiety) Death of cohabiting part- ner, same-sex partner, etc. (may result in disen- franchized