Pharmacotherapy
Pharmacotherapy is the treatment with the help of medicines (drugs). Psychopharmacology is the treatment of psychiatric disorders with the help of medicines (drugs). Medications used to treat psychiatric disorders are sometimes referred to as psychotropic drugs.
I. Antidepressants
Antidepressants are the drugs used to treat depressive disorders. There are various classes of antidepressants. Some of the most commonly used classes are-
a) SSRI’s: Selective Serotonin Reuptake Inhibitors
Drugs belonging to this class selectively blocks the reuptake of the neurotransmitter serotonin from the synaptic cleft (the space between 2 neurons), thereby increasing the serotonin concentration in the synapse. In depression there is serotonin deficiency- which causes low mood, negative thinking etc. So, these drugs correct the serotonin deficiency, leading to receptor downregulation & other intracellular changes.
Examples of this class of drugs are:
1. Fluoxetine: 10mg, 20mg, 40mg & 60mg capsules
2. Escitalopram: 5mg, 10mg, 15mg & 20mg tablets
3. Sertraline: 25mg, 50mg & 100mg tablets
4. Paroxetine: 12.5mg, 25mg & 37.5mg tablets
b) SNRIs: Serotonin Norepinephrine Reuptake Inhibitors
This class of drugs inhibits the reuptake of both Serotonin and Norepinephrine, thereby increasing the concentration of both in the synapse. Serotonin deficiency causes low mood, negative thinking etc. Norepinephrine deficiency causes decreased energy, interest, concentration etc. These can be corrected by SNRI group of drugs.
Examples of this class of drugs are:
1. Venlafaxine: 37.5mg, 75mg & 150mg tablets
2. Desvenlafaxine: 50mg, 100mg tablets
3. Duloxetine: 20mg, 30mg, 40mg, 60mg tablets
c) NDRIs: Norepinephrine–dopamine reuptake inhibitors
This class of drugs inhibits the reuptake of both Norepinephrine and Dopamine, thereby increasing the concentration of both in the synapse. Norepinephrine deficiency causes decreased energy, interest, concentration etc. Dopamine deficiency causes loss of happiness, joy, interest, pleasure etc. These can be corrected by NDRI group of drugs.
Examples of this class of drugs are:
1. Bupropion: 150mg, 300mg tablets
d) NaSSA: Noradrenergic Specific Serotonergic Antidepressant
This class of drugs by its α-antagonism, blocking of 5HT2A, 5HT2C & 5HT3 receptors causes increase in the concentration of both Norepinephrine & Serotonin. By its actions on H1 receptors causes sedation- so given at night.
Examples of this class of drugs are:
1. Mirtazapine: 7.5mg, 15mg & 30mg tablets
e) Classic antidepressants: Tricyclic Antidepressants
These are broad-spectrum antidepressants. These are the antidepressants which were initially discovered & used. But now these are not used so frequently as they may cause unwanted side-effects like sedation, dry mouth, orthostatic hypotension & cardiac arrhythmias.
Examples of this class of drugs are:
1. Clomipramine: 10mg, 25mg, 50mg & 75mg
2. Imipramine: 25mg, 75mg
3. Amitriptyline: 10mg, 25mg, 50mg & 75mg
II. Mood Stabilizers
These are the drugs which helps in stabilizing the mood & prevents mood fluctuations between depression & mania. Examples of some mood stabilizing drugs are-
1) Lithium: available as 300mg, 400mg SR tablets
Lithium is the classical mood stabilizer. It’s mechanism of action are various signal transduction sites beyond neurotransmitter receptors. This includes second messengers, such as the phosphatidyl inositol system, where lithium inhibits the enzyme inositol monophosphatase; modulation of G proteins; and regulation of gene expression for growth factors and neuronal plasticity by interaction with downstream signal transduction cascades, including inhibition of GSK-3 (glycogen synthase kinase 3) and protein kinase C.
2) Valproic acid: available as 200mg, 300mg, 400mg, 500mg tablets
Valproic acid is a mood stabilizing anti-convulsant. Mechanism of action: inhibiting voltage-sensitive sodium channels, boosting the actions of the neurotransmitter GABA (γ-aminobutyric acid), and regulating downstream signal transduction cascades.
3) Divalproex Sodium: available as 250mg, 500mg, 750mg & 1000mg tablets
Divalproex sodium is a stable coordination compound composed of sodium valproate & valproic acid in a 1:1 molar relationship.
4) Carbamazepine: available as 200mg, 300mg & 400mg tablets
Carbamazepine is also a mood stabilizing anti-convulsant. It’s mechanism of action is mainly by blocking of voltage sensitive sodium channels (VSSCs).
5) Lamotrigine: available as 25mg, 50mg, 100mg & 200mg tablets
Lamotrigine is also a mood stabilizing anti-convulsant which stabilizes mood from below- that is, it is more useful in preventing another episode of depression than mania.
Genetic Factors
1. Family Studies : If one parent has a mood disorder, the child will have a risk of 10-25% for mood disorder. If both parents have mood disorder, this risk doubles. The more members of the family are affected, the greater the risk is to a child. The risk is greater if the affected family members are first-degree relatives rather than more distant relatives.
2. Twin Studies : If one Monozygotic (identical) twin has a mood disorder, there is 70 to 90 percent risk that the other twin will develop the same disorder. In the case of Dizygotic (fraternal) twins, the risk is 16-35%.
III. Anxiolytics
Anxiolytics are the medicines used in anxiety disorders. Some most commonly used classes of drugs are-
a) Benzodiazepines
GABA (γ- aminobutyric acid) is a key neurotransmitter in anxiety and the benzodiazepine anxiolytics act upon this neurotransmitter system. Some of the drugs belonging to this group are-
1.Clonazepam: available as 0.25mg, 0.5mg, 1mg tablets
2.Lorazepam: available as 1mg, 2mg tablets
3.Diazepam: available as 5mg, 10mg tablets
b) Alpha-2-delta ligands
α2δ ligands bind to the α2δ subunit of presynaptic N and P/Q VSCCs (voltage-sensitive calcium channels), block the release of excitatory neurotransmitters such as glutamate when neurotransmission is excessive in the amygdala to cause fear and in CSTC circuits to cause worry.
1. Pregabalin: 75mg, 100mg, 150mg, 300mg tablets
2. Gabapentin: 100mg, 300mg, 400mg Capsules
c) β- Blockers
β- Blocker group of drugs acts on the β receptors to cut down the physical symptoms of anxiety, such as- palpitations, sweating, flushes, tremors etc and thus gives a feeling of wellbeing.
1. Propranolol LA: 40mg, 60mg, 80mg Capsules
d) SSRIs (Selective Serotonin Reuptake Inhibitors)
SSRIs are the mainstay in the treatment of anxiety disorders in the long run. They work by blocking the serotonin transporter (SERT) & thus increasing the serotonin levels, which are found to be deficient in anxiety disorders.
1. Paroxetine: 12.5mg, 25mg, 37.5mg tablets
2. Escitalopram: 5mg, 10mg, 15mg, 20mg tablets
3. Sertraline: 25mg, 50mg, 100mg tablets
e) SNRIs (Serotonin Norepinephrine Reuptake Inhibitors)
SNRIs along with SSRs are the main drugs for the longterm treatment of anxiety disorders. They block both the serotonin & norepinephrine transporters, thereby increasing the levels of both these neurotransmitters, which are found to be unbalanced in anxiety disorders.
1. Venlafaxine: 37.5mg, 75mg, 150mg tablets
2. Desvenlafaxine: 50mg, 100mg tablets
IV. Antipsychotics
This class of drugs are used in the treatment of Schizophrenia & other psychotic disorders, where there is an excess of the neurotransmitter Dopamine. Antipsychotics in general are dopamine receptor blockers, thereby reducing the dopamine levels, leading to downstream correction of deranged neuronal machinery.
a) Typical Antipsychotics (1st generation Antipsychotics)
They exert its action mainly by blocking D2 receptor of the neurotransmitter Dopamine.
1. Chlorpromazine: 25mg, 50mg, 100mg, 200mg tablets
2. Haloperidol: 0.5mg, 1.5mg, 5mg, 10mg tablets
3. Trifluoperazine: 5mg, 10mg tablets
4. Flupenthixol: 0.5mg, 1mg, 3mg tablets
b) Atypical Antipsychotics (2nd generation Antipsychotics)
This group of drugs, apart from its action on D2 receptors, also acts on other receptors like 5HT2A, 5HT1A, 5HT2C, 5HT3 etc and through some complex neuronal mechanisms deliver more Dopamine where it’s required and blocks excess dopamine action where it’s really excess, thereby contributing to its atypical mechanism of action.
1. Risperidone: 0.5mg, 1mg, 2mg, 3mg, 4mg tablets
2. Olanzapine: 2.5mg, 5mg, 7.5mg, 10mg, 15mg, 20mg tablets
3. Amisulpride: 50mg, 100mg, 200mg, 300mg, 400mg tablets
4. Aripiprazole: 5mg, 10mg, 15mg, 20mg, 30mg tablets
V. Drugs for Addiction
a) Nicotine
1. Nicotine Chewing Gums & Patches
Nicotine chewing gums & Patches are a part of substitution therapy. They deliver nicotine in a slow manner which does not produce the high & thus are not addicting.
2. Bupropion: 150mg, 300mg tablets
Bupropion is an NDRI, and it releases dopamine in the nucleus accumbens for the craving D2 receptors & thus reduces the craving.
3. Varenicline: 0.5mg, 1mg tablets
Varenicline is a selective α4β2-nicotinic acetylcholine receptor partial agonist, which causes sustained but small amounts of dopamine release (less than with nicotine).
b) Alcohol
1. Lorazepam: 1mg, 2mg tablets
Used during detoxification phase to control withdrawal symptoms
2. Acamprosate: 333mg tablets
Anti-craving agent, “artificial alcohol”, acts on glutamate system & GABA system
3. Naltrexone: 50mg
Blocks µ-opioid receptors, thus blocking the euphoria and “high” of heavy drinking.
4. Topiramate: 25mg, 50mg, 100mg tablets
An anticonvulsant, used as an anti-craving agent.
5. Baclofen: 10mg, 20mg, 30mg, 40mg
GABA agonist used as an anti-craving agent
6. Disulfiram: 250mg, 500mg tablets
Aversion agent, an aldehyde dehydrogenase inhibitor.
VI. Drugs for ADHD (Attention Deficit Hyperactivity Disorder)
a) Stimulants
Blocks both Dopamine & Norepinephrine transporter (DAT & NET) in specific circuits in the pre-frontal cortex, thereby ameliorating the symptoms of ADHD.
1. Methylphenidate: 10mg, 20mg tablets
b) Selective Norepinephrine Reuptake Inhibitor (selective NRI)
By selective blocking of NET in the prefrontal cortical circuits and not in the nucleus accumbens, restores the tonic DA & NE activity through D1 & α2A receptors.
1. Atomoxetine: 10mg, 18mg, 25mg tablets
c) Alpha-2A-adrenergic agonists
α-2a postsynaptic receptors are the primary receptors in the prefrontal cortex mediating the symptoms of ADHD. These drugs directly stimulate the receptors correcting the NE deficient neuronal networks, thus enhancing the signals.
1. Guanfacine: 1mg, 2mg, 3mg, 4mg
2. Clonidine: 100mcg
VII. Drugs for Dementia
a) Cholinesterase inhibitors
1. Donepezil: 5mg, 10mg, 11.5mg SR tablets
2. Rivastigmine: 1.5mg, 3mg tablets
3. Galantamine:4mg, 8mg tablets
b) NMDA Receptor Antagonist
1. Memantine: 5mg, 10mg, 7mg SR, 24mg SR tablets
Most of these psychotropic drugs are started on the lowest dose & is up-titrated based on the beneficial effect & any side-effects if any. Initial minor side effects if any like sedation will develop tolerance, and after a week or so may decrease/disappear. It may take a few weeks before appreciable benefits can be noted.