Antidepressants and anxiolytics target symptoms of depression and anxiety by increasing levels of monoamine neurotransmitters like serotonin, norepinephrine, and dopamine. There are several classes of these medications including tricyclic antidepressants, monoamine oxidase inhibitors, selective serotonin reuptake inhibitors (SSRIs), and serotonin-norepinephrine reuptake inhibitors (SNRIs). SSRIs are now commonly prescribed as first-line treatments due to their favorable side effect profiles compared to older classes. Proper use of antidepressants requires carefully adjusting doses over 4-8 weeks and monitoring patients for improvement in target symptoms.

1. ANTIDEPRESSANTS/ANXIOLYTICS
Dr. Basil B. Tumaini
MD, MMED Resident
December 2017
Psychiatry rotation
Muhimbili University of Health and Allied Sciences

2. Outline
 Background
 Target symptoms
 Classes of antidepressants
 Agents
 Indications for treatment
 SEs
 Rational use of antidepressants
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3. Background
 Late 1940s: striking elevation of mood to
some patients who were depressed and using
anti TB agent- iproniazid
 It was subsequently found to non selectively
and irreversibly inhibit the action of MAO –
Resulting in increase NT in postsynaptic
receptors
 This laid the foundation for the first and
durable monoamine theory of Affective
disorder i.e. depression – low levels of
monoamines
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4.  Not longer after chlorpromazine appeared in
the late 1950, antidepressant imipramine was
synthesized
 This was an attempt to find additional
compounds for the Rx of Schizophrenia
 It was soon learnt that imipramine was not
useful in treatment of psychotic sx but was
useful in treatment of depression in patients
with schizophrenias
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5.  This finding led to development of other
antidepressants
 Generally antidepressants are very effective,
and around 70% of people with major
depression start to feel better with the first
type of antidepressant they are prescribed
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6.  Antidepressant medication is often used in
association with individual psychological
therapy such as counseling and CBT
 When depression is part of BPD, a mood-
stabilizing medication may be prescribed to
reduce the frequency and severity of episodes
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7.  There is a range of antidepressants available
and it is generally thought that they have
similar effectiveness
 However, antidepressant drugs differ in their
likely side effects and their safety in overdose
 These are key considerations for a doctor
when deciding which drug to prescribe
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8.  There are differences in the way people
respond to each antidepressant drug
 The doctor may have to change the
medication to find one that works best for the
person concerned
 It may take between two to four weeks after
first taking medication before it starts to have
an antidepressant effect
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9. Target symptoms and duration of outcome
Target Symptoms Anticipated duration for outcome
Somatic symptoms 10 days to 2 weeks
Psychomotor 7-14 days after appropriate dose level
Mood Transitional mood, irritability/anger
3/4wks
Cognitive
functions
Improves with mood
Depressive
thoughts
Improves with mood BUT social and
individual factors are important
Psychotic Sxs Need antipsychotic medication
Social impairment Rehabilitation / psychotherapy03/12/2018 Antdepressants/anxiolytics 9

10. • Medical research and anecdotal observations
suggest that both the newer and old
antidepressants have equivalent therapeutic
effects
• The newer antidepressants have fewer side-
effects and a wider safety margin than the
older antidepressants
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11. Classification of Antidepressants
Traditionally, antidepressants are classified
according to
 Their structures e.g. Tricyclics, tetracyclics
 Effects on neurotransmission e.g. reuptake
inhibitors, oxidase inhibitors, receptors
antagonist
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12. Classes of antidepressants
 Heterocyclic antidepressants (Tricyclics,
tetracyclics)
 Monoamine oxidase inhibitors (MAOIs)
 Selective Serotonin reuptake inhibitors (SSRIs)
 Serotonin and noradrenaline reuptake
inhibitors (SNRIs)
 Norepinephrine and dopamine reuptake
inhibitors (NADRIs )
 Phenylpiperazines
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13. Drug groups Specific drugs Dose range (mg)
Heterocyclics Amitriptyline
Imipramine
Clomipramine
50 – 150 (150-300)
50 – 150 (150-300)
50 – 150 (150-300)
Monoamine oxidase
inhibitors
Phenelzine
Tranylcypromine
15-90
30-50
Phenylpiperazines Trazodone
Nefazodone
300-600
300-600
SSRI’s Fluoxetine
Fluvoxamine
Paroxetine
Citalopram
10-80
100-300
20-50
10-60
(SNRI’s) Venlafaxine 37.5-225mg
NADRI’s – Bupropion 150-30003/12/2018 Antdepressants/anxiolytics 13

14. Tricyclic Antidepressants
• Reuptake inhibitors of monoamines esp NE
and 5HT hence increasing potentiation of NE
and 5HT neurotransmission over time
• Have strong affinity for the cholinergic, alpha-
adrenergic and H1 receptors
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15. Tricyclic Antidepressants
• They have low affinity for the D receptors
hence are low potency medication
• Have a quinidine like effect (membrane
stabilizing effects ) hence impairs cardiac
conduction and toxicity in over dosage,
including convulsions
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16. TCAs
 Amitriptyline
 Imipramine
 Clomipramine
 Amoxapine
 Maprotiline
 Desipramine
 Nortriptyline
 Trimipramine
50 – 150 (150-300)
50 – 150 (150-300)
50 – 150 (150-300)
150-200
150-225
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17. Heterocyclics
 Rx - Depressive disorders
 Has anxiolytic properties hence useful in
anxiety related disorders
 None of the newer drugs are more
efficacious however their side effects
profiles have contributed to its major
drawback
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18.  Compliance is the major issue in treatment
failure
 Side effects tolerability – only in 1/4th of pts
 Side effects:
 Anticholinergic
 antihistamine
 5-HT activation
 adrenergic activation
 drug interactions
 Others: Seizures, decreased sexual
performance, triggering of mania, death when
over dosed
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19. Anticholinergic
 Dry mouth, blurred vision, constipation,
urinary hesitancy, toxic confusional states
 Limitations in asthma and angle closure
glaucoma
 Alternative: SSRI’s, Bupropion (Dopamine/NE
Reuptake Inhibitor)
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20. Antihistamine
 Drowsiness, fatigue (hyper-somnia)
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21. 5-HT activation
• Cognitive effects: confusion, hypomania,
hallucinations, agitation, headache, coma
• Autonomic effects: shivering, sweating, fever,
hypertension, tachycardia, nausea, diarrhea
• Somatic effects: myoclonus/clonus (muscle
twitching), hyperreflexia, tremor
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22. Adrenergic activation
• Tremor, excitement, palpitation, orthostatic
hypotension, weight gain, quinidine like
effects
• Baseline ECG - standard of care
• limitations in cardiac arrhythmias and CCF
• Alt: SSRI’s, Bupropion
• Others: Seizures, decreased sexual
performance, triggering of mania, death when
over dosed
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23. Monoamine oxidase inhibitors
 Irreversible non specific inhibition MAOA and B
 Rx of atypical depression, panic disorder, non-
responders with other drugs
 Insomnia and day time stimulation
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24. Monoamine oxidase inhibitors
 Adverse effects profile requires provision of
more information when prescribing and
exploration of compliance
• 85% inhibition for effects (platelets
monitoring)
• Their life threatening adverse effects limit
their use in clinical practice
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25. Monoamine oxidase inhibitors
 Phenelzine 45-90
 Tranylcypromine 30-50
 Moclobemide
 Selegiline
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26. MAOI AEs
 Some of those of TCAs
 Anticholinergic
 5-HT and adrenergic activation
 MAOI specific
 Paraesthesia
 insomnia
 pedal edema
 Hypertensive crisis
 Drug interactions
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27. Hypertensive crisis
 Tyramine containing foods (Fava beans, beer,
red wines, liver, smoked meat, yeast, chocolate,
etc)
 Sympathomimetic amines (OTC drugs e.g.
Pseudoephedrine) should be avoided
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28. Drug interactions
 narcotics (stop MAOI 3/52 prior to elective
surgery
 Fatalities reported with meperidine and
fluoxetine – Medic Alert Bracelets suggested
 Chlorpromazine (50mg), phentolamine and other
alpha blocking agents good in MAOI related
emergencies; peripheral vasodilators also useful
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29. NADRI’s
 Bupropion (300-450 mg daily) – Low tolerance
of side effects as compared to those of of
Heterocyclic's
 Advantage in absence of CVS effects and no
significant orthostatic hypotension
 Also no sexual Side effects, weight gain or day
time drowsiness
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30. NADRI
Adverse effects:
 Restlessness, agitation, anxiety and
insomnia
sufficient intensity to discontinue in
about 2%
 Greater CNS lowering of seizure threshold
effects hence avoid in epileptics
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31. Phenylpiperazines
 Potent antagonists of 5-HT2 receptors;
inhibit pre-synaptic 5-HT reuptake, and NE
for nefazodone
 Lack quinidine effects on the heart
Safer when taken alone in Overdose than
the TCA’s, but synergistic effect with CNS
depressants including alcohol
 Useful in depression with agitation and
aggression associated with AOBS
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32. Phenylpiperazines AEs
 Arrhythmogenic
 Premature ventricular couplets (VC’s) and
episodic tachycardia
 Caution in heart block. These adverse
effects are less with nefazodone
 Sedation and orthostatic hypotension (the
latter less so with nefazodone)
 Drug interactions with some drugs metabolized
through Cyt. P450 system as they are inhibitory
(more so for nefazodone)
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33. SSRIs
 Specifically inhibit reuptake of 5HT in
presynaptic receptor
 Used in treatment of Depressive, obsessive
compulsive and eating disorders
 Widely prescribed
 Single dosing improves compliance
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34. SSRIs
 Minimal side effects of adrenergic, muscarinic,
histaminergic, and serotonergic receptors
better side effects profile
 Effective at low doses (75% respond)
 BUT expensive for Tanzania
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35. SSRIs
• Fluoxetine 10-80
• Fluvoxamine 100-300
• Citalopram
• Paroxetine
• Sertraline
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36. SSRIs AEs
 Low risk of anticholinergic effects
 CNS and extra pyramidal effects of
insomnia, psychomotor agitation, tremor
and headache
 GI effects of nausea and diarrhea
 Serotonin activation – palpitations,
agitation, muscle twitching, delirium
 Some inhibition of Cytochrome P450
isoenzymes contributes to drug
interactions
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37. SNRIs
 Venlafaxine (Effexor) 75 – 300 mg
 Venlafaxine is a bicyclic antidepressant
 usually categorized as a serotonin-
norepinephrine reuptake inhibitor (SNRI), but
it has been referred to as a serotonin-
norepinephrine-dopamine reuptake inhibitor
 Venlafaxine inhibits the neuronal uptake as
serotonin at low doses and nor epinephrine
and dopamine at higher doses
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38. SNRI’s
 Its main indication is for the treatment of
MDD, but its slow-release formulation was
approved for anxiety disorders
 Potential effects of inducing mania in BPD
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39. SNRIs
 Side effects profile like those of SSRI’s
including hyper stimulation, sexual
dysfunction and transient withdrawal Sx
 Has no association with weight gain, no
cardiac conduct problems and no sedation
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40. Clinical uses of antidepressants
 Depression
– Major depressive disorder
– Persistent depressive disorder
– Mood disorder due to a general medical condition
(depression)
– Adjustment disorder (with depressed mood)
– BPD (currently depressed)
– Cyclothymic disorder
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41. Clinical uses of antidepressants
• Relapse prevention in recurrent non bipolar
depression
• Atypical depression (romantic preoccupation
and disappointments in relationships,
hyperphagia, herpersomnia, and body fatigue
– MAOIs Phenelzine)
• Obsessive Compulsive Disorder
(Clomipramine, SSRI- Fluoxetine, Paroxetine)
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42. Clinical uses of antidepressants
• Panic disorder (Imipramine)
• Eating Disorders (Bulimia Nervosa – fluoxetine
at 80mg per day)
• ADHD in children ( Imipramine)
• Generalized pain syndrome (Tricyclics)
• Enuresis in children ( Imipramine)
• Premature ejaculation (SSRI)
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43. Rational use of antidepressants
 SSRI are recommended to be used as a first line
treatment while others should be reserved for
non responders
 Doses should be carefully adjusted and each drug
trial should be 4-8 weeks
 Improvement should be monitored by following
up target Sx
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44. Rational use of antidepressants
 Therapeutic effectiveness may require
about 2-4 weeks though side effects will
appear within few days
 Pts with cardiac problems should be given
SRI and other newer drugs – bupropion
than Heterocyclis and related groups
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45. Rational use of antidepressants
 AD are not necessary in patients with grief
reactions or adjustment disorders with
depressed mood because they are self
limiting
 When possible, SSRI should be tapered off
except fluexetine which has got a long
acting effects
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46. Rational use of antidepressants
 Heteroyclics especially TCA should be
tapered off slowly (within weeks to
months) due to withdrawal effects
 Co administration of two different AD does
not boost efficacy and will worsen side
effects
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47. Benzodiazepines
 Diazepam
 Midazolam
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52. BB: Propranolol
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