Tricyclic antidepressants

Question 1

describe the activity of the monoamine reuptake inhibitors

Answer 1

generally TCAs and SSNRIs block NET &SERT. SSRI only block the SERT (initially increase the monoamine in the synaptic cleft, then decrease it due to a2 receptor activation, then due to this receptors desensitization, the -ve feedback receptors downregulate, increasing the concentration of the monoamines in the synaptic cleft.

Question 2

name the 3 types of monoamine reuptake inhibitors

Answer 2

1. TCA
2. SSRI
3. SSNRI

Question 3

Treatment of depression & aim

Answer 3

treatment:

1. monoamine reuptake inhibitors (SSRIs first line)
2. a2 & 5HT2a antagonists
3. melatonin MT1& 2 agonist
4. MAOi

treatment scheme:
first line SSRIs–> but has side effect (anxiety before the antidepressant effect) –> so give BZD then slowly discontinue them until the SSRIs antidep effect develops (after 2-3 weeks)–> if no effect 4-6 weeks–> dose elevation–> if not effective again –> adjuvant treatment, medicine switch or augmentation

aim:

1. first weeks: relief of acute symptoms
2. months: prevention of relapse- maintenance therpay
3. years: prevention of repeated episodes- prophylactic treatment

Question 4

name 3 TCAs

Answer 4

1. imipramine (noctural eneuresis& anxiety disorder)
2. amitryptylline (neuropathic pain & migrane profilaxis)
3. desipramine
4. clomipramine (OCD &neuropathic pain) -strong SERT inhibition almost acts as SSRI-
   - ->all are tricyclic antidepressants
5. maprotylline (NET>SERT): Tetracyclic antidepressant
6. Bupropion is unicyclic antidepressant NET and weekly DAT. (stupor depression and smoking cessation, CI in epilepsy bec it has an amphetamine like structure)

Question 5

indications of TCA (5)

Answer 5

1. Depression (not first line due to side effects)
2. anxiety disorder (panic disorder and OCD)
3. neuropathic pain
4. night-time urinary incontinence (noctural eneuresis)
5. migrane profilaxis

generally TCA need 2-3 weeks or a month in order to see their effects. They have a duration of 25-35 hours so they need to be taken only once per day.

–> administration is oral

Question 6

side effects of TCA (5)

Answer 6

1. Blocks a1: orthostatic hypotension& reflex tacchycardia
   H1: sedation, dizziness, confusion,weight gain
   M: dry mouth,urinary retention, constipation, tacchycardia and blurred vision.

(TCA,3’C’,Comma, Convulsions, Cardiotoxicity)

2. Blocks K+ channels (HERG) : at very high dose causing ventricular arrythmias.
3. interacts with alcohol and increases its depressive respiratory effects.
4. when taken with MAOi, increases SE level causing serotonin syndrome ( fever, seizures, comma, muscle cramps, hypertension)
5. prevents antihypertensive actions of a2 AG and guanethidine