DRUGS USED TO TREAT AFFECTIVE

DISORDERS - DEPRESSION & BIPOLAR

SYNDROME
Dr. Pashmina Fayyaz
Lecturer STMU
AFFECTIVE DISORDERS
 Disorders that are related to mood

 Mainly include:
- Depression
- Mania
- Bipolar syndrome

 Others:
- Seasonal Affective disorder
- Adjustment disorder
- Dysthymia; persistent depressive disorder (PDD)
DEPRESSION
Form of mental illness; intense feelings of sadness and despair increased in both
intensity and duration to a devastating extent

Characterized by:
- General dysphoric mood
- General lack of interest in previously pleasurable activities
- Anorexia, sleep disorders
- Fatigue, lack of self-esteem
- Somatic complaints, and irrational guilt
- Recurrent thoughts of death and suicide may also help lead to a diagnosis of
depression
Cont..
 Lifetime risk:
10-20% for women
5-12% for men
 Family history of Depression increases risk 1.5-3 times
 Up to 20%-25% of patients with major medical comorbidity will develop
Depression
 Other causes: recent stressful incident, misfortune or illness may exacerbate an
episode of depression
 Average age of onset is in mid-20’s
(Depression must not be confused with other mental disorders that may also influence
mood and disorder e.g. Schizophrenia)
Pathophysiology of Affective disorders

Monoamine Theory of Mental Depression

 Depression is linked to low levels of norepinephrine and/or serotonin.

 Mania is linked to high levels of norepinephrine and/or serotonin.

 Bipolar mood disorder is alternating cycles of depression and mania.

Pathophysiology of Depression
 Disturbance in CNS neurotransmission of amine neurotransmitters
 5-hydroxytryptamine (serotonin), norepinephrine, and dopamine; control many aspects of
mood and behavior.
 This disturbance may be caused by an increased sensitivity of the presynaptic or
postsynaptic receptors for these transmitters (particularly norepinephrine & serotinin)
 In such case Antidepressant drugs given; which prolong the activity of amine
neurotransmission in the brain, thereby causing a compensatory decrease in the sensitivity
of the amine receptors (Down-regulation). As receptor sensitivity decreases, symptoms of
depressions are resolved
 Latency period; time lag for drug to show effects from the time it is initiated: 2 to 4 weeks;
time needed for compensatory change in receptor sensitivity to take place
 Increased levels of Glucocorticoids (Cortisol) in people with depression
Treatment
 Medications
 Psychotherapy
 Other
 ECT
 Light therapy – primarily for SAD
Anti-depressants drugs
 Drugs that increase the level of norepinephrine and serotonin are used in the
treatment of depression.

 Major antidepressant drug classes:

 Tricyclic antidepressants (TCAs)
 Monoamine oxidase inhibitors (MAOIs)
 Second generation drugs

All three groups attempt to increase aminergic transmission/increasing presence of

amine transmitters in synaptic cleft but by different mechanisms
 Tricyclic
antidepressants

Mono-amine
Anti depressant
Oxidase
drugs Inhibitors (MAO)
Selective Serotonin
Reuptake Inhibitors
(SSRIs)
Second generation
drugs Serotonin/Nor-
epinephrine Inhibitors
(SNRIs)
a) Tricyclic Antidepressants

 Three-ring chemical structure (hence the name “tricyclic”)

 Block the reuptake of amine neurotransmitters into the presynaptic terminal; but
are nonselective
 This allows the released amines to remain in the cleft and continue to exert their
effects (especially norepinephrine); leads to the compensatory decrease in
receptor sensitivity, which ultimately leads to a decrease in depression
b) MAO Inhibitors

 Monoamine Oxidase (MAO) is an enzyme that is located at the amine synapses

and helps remove released transmitters through enzymatic destruction
 MAO enzyme exists in 2 forms:
 MAO-A: inhibition of which may be desirable in treating depression; as this
subtype does destruction of Serotonin and N/E
 MAO-B: prolongs effect of Dopamine in Parkinson’s disease

* Not drug of choice but helpful if other agents do not respond.

c) Second Generation Drugs
 Selective Serotonin Reuptake Inhibitors (SSRIs)*
 Serotonin/Nor-epinephrine Reuptake Inhibitors (SNRIs)

SSRIS:
These drugs block selective re-uptake of serotonin
• Flouxetine
• Citalopram
• Paraxetine
• Sertraline
* Less side effects; helpful in long term Rx of depression; also serves as initial method of Rx
Other selective drugs

 Reboxetine – selectively inhibits reuptake of nor-epinephrine

 Venalfexine – selectively inhibit serotonin & nor-epi (SNRIs)/ no effect on
dopamine synapses
Adverse effects
 Tricyclics:

 Sedation
 Anticholinergic:
- Central: confusion, delirium
- Peripheral: dry mouth, constipation, urinary retention, tachycardia.
• Arrythmia
• Orthostatic hypotension
 Highest potential for fatal overdose; caution in patients with history of suicidal
thoughts
 Cont..
 MAO Inhibitors:

 In contrast to Tricyclics, these cause CNS excitation

 Central & peripheral anticholinergic effects (lesser extent)
 Sytemic MAO inhibition – no more breakdown of catecholamines 
Increased blood pressure
 Fermented food: cheese & wine (contains tyramine)– Tyramine stimulate
release of Catecholamine and MAO inhibitors reduce its breakdown/do not
degrade it – leads to HTN crisis (due to excessive catecholamine levels)
Cont..

 SSRIs:
 Less sedation, anticholinergic and cardiovascular effects
 GI problems
 Serotonin syndrome: sweating, shivering, movement disorders
(typically disappear when drug discontinued)
Use of Anti Depressants in Chronic Pain

 Neuropathic pain
 Fibromyalgia
 Chronic low back pain
 Migraine

 Amitryptaline (tricyclic agents)

 Nortryptaline (tricyclic agents)
 Paroxetine (SSRI)
 Venlafexine (SNRI)
MANIA
An abnormally elevated mood state characterised
by symptoms such as:
 Inappropriate elation
 Increased irritability
 Increased speed and/or volume of speech
 Increased energy and activity level
 Poor judgment
 Inappropriate social behaviour

* A maniac episode is not a disorder in itself but rather it is a part of bipolar

disorder.
* Hypomania: A milder form of mania; the patient is able to carry on with their
day-to-day lives and never lose touch with the reality
BIPOLAR DISORDER
 Bipolar syndrome is associated with
mood swings from one extreme
(mania) to the other (depression)
 10% of all patients with depression
exhibit bipolar syndrome
Treatment of Bipolar
Disorder: Antimanic drugs
 Manic episodes are characterized by euphoria, hyperactivity, and talkativeness
and depressive episodes.
 Increased NT release - for the manic episodes of this disorder. The subsequent
depression may simply be a rebound from the general excitement of the manic
episode
Lithium

 Lithium (Li) is a monovalent cat-ion - competing with other cat-ions including

sodium, potassium, and calcium.
 Lithium may stabilize neuronal excitability by decreasing the sensitivity of
certain postsynaptic receptors. It increases the effects of Serotonin and GABA.
 During a maniac episode a serum concentrations between 1.0-1.4 mEq/L is
desirable.
Lithium toxicity
Mild (Below 1.5 mEq/L)
 Fine hand tremor (resting)
 Gastrointestinal upset
 Muscle weakness
 Fatigue
 Problems with memory and concentration
Moderate (1.5–3.0 mEq/L)
 Confusion, Lethargy
 Ataxia
 Dysarthria
 Emesis
 Increased deep tendon reflexes
 Increased tremor
 Muscle fasciculation
Severe (Above 3.0 mEq/L)
 Choreoathetoid movements
 Seizures
 Respiratory complications
 Coma
 Death
Other drugs used in bipolar syndrome

 Antiseizure medications - Carbamazepine, Valporic acid, gabapentin and

Lamotrigine
 Antipsychotic medications - Clozapine and Resperidone