What is nortriptyline used for. How does nortriptyline work in the body. What are the potential side effects of nortriptyline. Is nortriptyline safe during pregnancy. How is nortriptyline administered.

Understanding Nortriptyline: A Versatile Antidepressant

Nortriptyline is a tricyclic antidepressant (TCA) that has been used for decades to treat various conditions. While primarily indicated for depression, this medication has shown efficacy in managing several off-label conditions as well. To fully grasp the significance of nortriptyline in modern medicine, it’s crucial to explore its uses, mechanism of action, and potential side effects.

FDA-Approved and Off-Label Uses of Nortriptyline

The Food and Drug Administration (FDA) has approved nortriptyline for the treatment of depression in adults. However, healthcare providers often prescribe this medication for other purposes based on clinical experience and research. Some of the off-label uses include:

• Chronic pain management
• Diabetic neuropathy
• Myofascial pain
• Trigeminal neuralgia
• Postherpetic neuralgia
• Smoking cessation
• Migraine prophylaxis
• Neurogenic cough

Is nortriptyline effective for these off-label uses. While research supports its efficacy in many of these conditions, the level of evidence varies. For instance, studies have shown promising results in managing neuropathic pain and aiding smoking cessation. However, more research may be needed to fully establish its effectiveness in some of the other off-label uses.

The Complex Mechanism of Action Behind Nortriptyline

Nortriptyline’s therapeutic effects stem from its complex interactions with various neurotransmitter systems in the brain. Understanding these mechanisms can provide insight into why this medication is effective for diverse conditions.

Neurotransmitter Reuptake Inhibition

The primary mechanism of action for nortriptyline involves inhibiting the reuptake of two key neurotransmitters:

1. Serotonin
2. Norepinephrine

By blocking the reuptake of these neurotransmitters, nortriptyline increases their concentration in the synaptic cleft, enhancing neurotransmission. This action is believed to be responsible for its antidepressant effects.

Additional Pharmacological Actions

Beyond neurotransmitter reuptake inhibition, nortriptyline exhibits several other pharmacological effects:

• Inhibition of histamine activity
• Blockade of 5-hydroxytryptamine receptors
• Anticholinergic effects
• Modulation of adrenergic responses

How do these additional actions contribute to nortriptyline’s effects. The diverse receptor interactions may explain its efficacy in treating various conditions beyond depression. For instance, its effects on norepinephrine levels may play a role in pain management, while its impact on acetylcholine could contribute to side effects like dry mouth.

Pharmacokinetics: The Journey of Nortriptyline in the Body

Understanding how nortriptyline is processed in the body is crucial for optimal dosing and minimizing potential side effects. Let’s explore the key pharmacokinetic properties of this medication.

Absorption and Distribution

When taken orally, nortriptyline reaches peak plasma concentrations after 7 to 8.5 hours. However, its full antidepressant effects may not be apparent for several weeks. The medication is widely distributed throughout the body, including the brain, heart, and liver. Notably, nortriptyline and its metabolites bind strongly to plasma and tissue proteins.

Metabolism and Excretion

Nortriptyline undergoes significant first-pass metabolism in the liver, primarily by the enzyme CYP2D6. This metabolism can lead to variations in drug levels between individuals, especially those with genetic differences in CYP2D6 activity. The primary route of elimination is through urine, with about one-third of the dose excreted as metabolites within 24 hours. Some excretion also occurs through feces via bile.

Why is understanding nortriptyline’s metabolism important. Variations in metabolism can affect drug levels and efficacy. Patients who are “poor metabolizers” due to genetic factors may require lower doses to avoid toxicity, while “rapid metabolizers” might need higher doses for therapeutic effect.

Proper Administration of Nortriptyline: Dosage and Formulations

Correct administration of nortriptyline is crucial for achieving therapeutic benefits while minimizing side effects. Healthcare providers typically tailor the dosage to individual patient needs.

Available Formulations

Nortriptyline is available in two main formulations:

1. Oral capsules: 10 mg, 25 mg, 50 mg, and 75 mg strengths
2. Oral solution: 10 mg/5 mL (473 mL)

Typical Dosing Regimens

The usual adult dosage for nortriptyline is 25 mg taken three or four times daily. However, treatment often begins at a lower dose and is gradually increased as needed. Some key points about nortriptyline dosing include:

• The total daily dosage can sometimes be administered once daily
• Doses higher than 100 mg daily require monitoring of plasma nortriptyline levels
• Doses exceeding 150 mg daily are not recommended

How should nortriptyline dosage be adjusted for specific populations. Patients with hepatic or renal impairment may require dose adjustments, although specific guidelines are not provided in the manufacturer’s labeling. Careful monitoring and potential dose reduction are advisable in these populations.

Potential Side Effects and Safety Considerations of Nortriptyline

While nortriptyline can be highly effective, it’s essential to be aware of potential side effects and safety considerations. Understanding these can help patients and healthcare providers make informed decisions about treatment.

Common Side Effects

Nortriptyline, like other tricyclic antidepressants, can cause various side effects. Some of the more common ones include:

• Dry mouth
• Constipation
• Blurred vision
• Urinary retention
• Drowsiness
• Weight gain
• Dizziness

Are these side effects typically severe. While often mild, these effects can be bothersome for some patients. In many cases, they may diminish over time as the body adjusts to the medication.

Serious Adverse Effects

While less common, some serious adverse effects can occur with nortriptyline use:

• Cardiac arrhythmias
• Seizures
• Serotonin syndrome (when combined with other serotonergic medications)
• Increased risk of suicidal thoughts, especially in young adults and adolescents

How can the risk of serious side effects be minimized. Close monitoring, especially during the initial treatment period, is crucial. Patients should be educated about potential warning signs and encouraged to report any concerning symptoms promptly.

Nortriptyline in Special Populations: Pregnancy, Breastfeeding, and Pediatrics

The use of nortriptyline in certain populations requires special consideration due to potential risks and limited data on safety and efficacy.

Pregnancy Considerations

The use of nortriptyline during pregnancy is a complex decision that requires careful weighing of potential risks and benefits. Some key points to consider include:

• Preclinical studies have shown potential risks to the fetus
• Limited human data is available on the safety of nortriptyline during pregnancy
• Untreated depression during pregnancy also carries risks

What approach should be taken regarding nortriptyline use in pregnancy. Healthcare providers typically assess the individual situation, considering the severity of depression, alternative treatments, and potential risks to both mother and fetus. In some cases, the benefits of continuing treatment may outweigh the potential risks.

Breastfeeding Considerations

Nortriptyline is present in breast milk, raising concerns about potential effects on nursing infants. Points to consider include:

• The amount of drug transferred to breast milk is generally low
• Limited data suggests minimal risk to most infants
• Monitoring of the infant for potential side effects is recommended

Can women taking nortriptyline safely breastfeed. In many cases, the benefits of breastfeeding outweigh the potential risks of nortriptyline exposure. However, each situation should be evaluated individually, considering factors such as the infant’s age and health status.

Pediatric Use

Nortriptyline is not FDA-approved for use in children. However, it is sometimes used off-label in pediatric populations. Considerations for pediatric use include:

• Limited data on efficacy and safety in children
• Potential for increased risk of suicidal thoughts in young people taking antidepressants
• Need for close monitoring if used in pediatric patients

Under what circumstances might nortriptyline be considered for pediatric use. In cases where other treatments have failed and the potential benefits are deemed to outweigh the risks, nortriptyline might be considered. However, this decision should be made carefully, with thorough discussion between healthcare providers and families.

Drug Interactions and Precautions with Nortriptyline

Nortriptyline can interact with various medications and substances, potentially altering its effectiveness or increasing the risk of side effects. Understanding these interactions is crucial for safe and effective treatment.

Common Drug Interactions

Some medications and substances that can interact with nortriptyline include:

• Monoamine oxidase inhibitors (MAOIs)
• Other serotonergic drugs (e.g., SSRIs, SNRIs)
• CYP2D6 inhibitors (e.g., certain antipsychotics, antiarrhythmics)
• Alcohol
• Anticholinergic medications

How can these interactions affect treatment? Some interactions may increase the risk of side effects, while others might reduce the effectiveness of nortriptyline. For instance, combining nortriptyline with MAOIs can lead to potentially dangerous increases in serotonin levels.

Precautions and Contraindications

Certain conditions may increase the risks associated with nortriptyline use. Precautions should be taken in patients with:

• Cardiovascular disease
• History of seizures
• Angle-closure glaucoma
• Urinary retention
• Hepatic or renal impairment

What steps can be taken to mitigate risks in these populations? Careful monitoring, dose adjustments, and consideration of alternative treatments may be necessary. In some cases, such as recent myocardial infarction, nortriptyline may be contraindicated.

Monitoring and Managing Nortriptyline Therapy

Effective use of nortriptyline requires ongoing monitoring and management to ensure optimal therapeutic outcomes and minimize risks.

Therapeutic Drug Monitoring

Monitoring plasma levels of nortriptyline can be beneficial, especially at higher doses. Key points include:

• Therapeutic range is typically considered to be 50-150 ng/mL
• Levels above 150 ng/mL may increase the risk of toxicity
• Individual response can vary, and some patients may benefit from levels outside this range

When should therapeutic drug monitoring be considered? It’s particularly useful when prescribing doses above 100 mg daily, in patients with hepatic impairment, or when there’s concern about potential drug interactions affecting nortriptyline levels.

Managing Side Effects

Strategies for managing common side effects of nortriptyline may include:

• Gradual dose titration to improve tolerability
• Adjusting the timing of doses (e.g., taking at bedtime to minimize daytime drowsiness)
• Using supportive measures (e.g., increasing fluid intake for dry mouth)
• Considering dose reduction if side effects are persistent and bothersome

How can patients be empowered to manage side effects? Education about potential side effects, coping strategies, and the importance of communication with healthcare providers is crucial. Patients should be encouraged to report persistent or concerning symptoms promptly.

Long-Term Management

For patients on long-term nortriptyline therapy, ongoing management is essential. This may involve:

• Regular assessment of therapeutic efficacy
• Monitoring for emergence of new side effects
• Periodic review of the need for continued treatment
• Consideration of gradual dose reduction or discontinuation when appropriate

What factors should guide decisions about long-term nortriptyline use? The individual’s response to treatment, overall health status, and the presence of any ongoing risk factors or side effects should all be considered. In some cases, long-term maintenance therapy may be beneficial, while in others, a limited course of treatment may be sufficient.

In conclusion, nortriptyline remains a valuable tool in the treatment of depression and various other conditions. Its complex mechanism of action, coupled with its long history of use, provides healthcare providers with a versatile option for managing a range of disorders. However, the use of nortriptyline requires careful consideration of individual patient factors, potential side effects, and necessary monitoring. By understanding these aspects, healthcare providers can optimize the use of nortriptyline, potentially improving outcomes for patients struggling with depression and other challenging conditions.

Nortriptyline – StatPearls – NCBI Bookshelf

Continuing Education Activity

Nortriptyline is indicated for use in the treatment of depression (FDA-approved). It can also be used off-label for conditions such as chronic pain, diabetic neuropathy, myofascial pain, orofacial pain, and postherpetic neuralgia. Nortriptyline has also shown to be useful in patients trying to quit smoking. Nortriptyline is not FDA approved for use in children. This activity covers nortryptyline’s indications, mechanism of action, pharmacology, administration, adverse event profiles, eligible patient populations, contraindications, and monitoring, and highlights the role of the interprofessional team in the management of depression and other diseases with nortriptyline therapy.

Objectives:

• Outline the mechanism of action of nortriptyline.

• Review the indications for using nortriptyline.

• Summarize the potential adverse effects associated with nortriptyline therapy.

• Describe the importance of improving care coordination among the interprofessional team to enhance the delivery of care for patients who can benefit from therapy with nortriptyline.

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Indications

Nortriptyline is indicated for use in the treatment of depression (FDA-approved). Nortriptyline is not FDA approved for use in children.

Nortriptyline can also be used for the following off-label indications:

• Chronic pain[1] 

• Diabetic neuropathy[2]

• Persistent myofascial pain[3]

• Trigeminal neuralgia[4]

• Postherpetic neuralgia[5]

• Smoking cessation[6]

• Migraine prophylaxis[7]

• Neurogenic cough[8]

Mechanism of Action

Nortriptyline is an antidepressant that falls under the pharmacological category of tricyclics (secondary amine), more commonly known as TCAs.The consensus is that nortriptyline inhibits the reuptake of serotonin and norepinephrine by the presynaptic neuronal membrane, thereby increasing the concentration of those neurotransmitters in the synapse. Additionally, nortriptyline inhibits the activity of histamine, 5-hydroxytryptamine, and acetylcholine. Nortriptyline increases the pressor effect of norepinephrine but hinders the pressor response of phenethylamine. However, research has found additional receptor effects, including desensitization of adenylyl cyclase, down-regulation of beta-adrenergic receptors, and downregulation of serotonin receptors. 

The proposed mechanism of nortryptyline in neuropathic pain is an increase in noradrenaline levels acting within dorsal root ganglia on β2-adrenoceptors expressed by non-neuronal satellite cells. This stimulation of β2-adrenoreceptors reduces the neuropathy-induced production of TNFα, resulting in the relief of neuropathic pain.[9] Nortriptyline’s mechanism in smoking cessation is unclear, but the possible action may involve simulating the noradrenergic actions of nicotine.[10] A recent study suggests that nortriptyline can be used as a new antimicrobial drug against multidrug-resistant Candida Albicans infection by inhibiting biofilm and ability to kill cells in a mature biofilm efficiently; however, more research is needed. [11]

Pharmacokinetics

• Absorption: Peak plasma concentrations are 7 to 8.5 hours after oral administration, although antidepressant action is obtained after a few weeks.[12]

• Distribution: Nortriptyline is distributed to the brain, heart, and liver. Nortriptyline and its metabolite are highly bound to plasma and tissue proteins. Nortriptyline crosses the placenta, and nortriptyline is present in breast milk.[13]

• Metabolism: Nortriptyline, when administered orally, undergoes first-pass metabolism in the liver by CYP2D6.[14]

• Excretion: The primary route of elimination is urinary excretion, approximately one-third of the dose as metabolites within 24 hours, but it is also excreted in feces via the bile.

Administration

Nortriptyline is usually taken orally as a capsule or an oral solution. Capsule form comes in 10 mg, 25 mg, 50 mg, and 75 mg strengths. The oral solution form is usually of the following composition 10 mg/5 mL (473 mL).  The usual adult dose is 25 mg three or four times daily; it should begin at a low level and increase as needed. As an alternate regimen, the total daily dosage can be given once daily. When doses higher than 100 mg daily are administered, plasma levels of nortriptyline should be monitored. Doses higher than 150 mg daily are not recommended.

Use in Specific Patient Population

• Patients with Hepatic impairment: No information has been provided in the manufacturer’s product labeling. However, caution and dose reduction are advised in patients with hepatic impairment, given the drug’s primary metabolism is by liver enzymes.[14]

• Patients with Renal impairment: No information has been provided in the manufacturer’s product labeling. 

• Pregnancy Considerations: According to product labeling, preclinical studies during pregnancy have been inconclusive. Safe use of nortriptyline during pregnancy has not been established; therefore, when the drug is administered to pregnant patients or women of childbearing potential, clinicians must weigh the potential benefits against the possible hazard.

• Breastfeeding Considerations: According to product labeling, the safe use of nortriptyline during lactation has not been established. However, nortriptyline’s concentration in breastmilk is low. Consequently, amounts ingested by the infant are small. However, the less active metabolites are often detectable in low levels in infant serum. Many reviewers consider nortriptyline preferred TCA during breastfeeding; however, drugs that have a better safety profile during lactation are paroxetine and sertraline.[13]

Adverse Effects

Nortriptyline has a black box warning for increased risk of suicide in adolescents, children, and young adults with major depressive disorder and multiple other psychiatric disorders.[16]

The most common adverse effects of nortriptyline include downiness, xerostomia, dizziness, constipation, blurred visions, palpitations, tachycardia, impaired coordination, increased appetite, nausea/vomiting, diaphoresis, weakness, disorientation, confusion, restlessness, insomnia, anxiety/agitation, urinary retention, urinary frequency, rash, urticaria, pruritus, weight gain, libido changes, impotence, gynecomastia, galactorrhea, tremor, hypo/hyperglycemia, paraesthesia, and photosensitivity. [17]

The most serious adverse effects include orthostatic hypotension, HTN, syncope, ventricular arrhythmias, AV block, MI, stroke, paralytic ileus, glaucoma, increased IOP, agranulocytosis, leukopenia, thrombocytopenia, hepatitis, angioedema.[18][19]

Neuropsychiatric adverse drug reactions include EPS symptoms, ataxia, tardive dyskinesia, hallucinations, psychosis exacerbation, hypomania/mania, exacerbation of depression, suicidality, serotonin syndrome, SIADH, hyperthermia, and seizures.[20][21][22]

Cardiotoxicity is the hallmark adverse drug reaction of tricyclic antidepressants, such as nortriptyline. In the case of TCA toxicity, fast cardiac sodium channels are inhibited, which can lead to cardiac arrhythmias. On electrocardiography. A widened QRS complex is often noted.[23]

A patient can also have withdrawal symptoms such as dizziness, gastrointestinal problems such as nausea and vomiting, anxiety, headaches, and restlessness if the patient discontinues nortriptyline abruptly. Clinicians can avoid these withdrawal symptoms by gradually decreasing the dose of nortriptyline over a period.[24]

Drug Interactions

Clinicians should avoid concurrent usage of cimetidine and tricyclic antidepressants such as nortriptyline as the drug interaction can increase the concentration of TCAs. Using nortriptyline, along with alcohol, can increase the effects of alcohol on patients. Cytochrome P450 2D6 metabolizes nortriptyline. All pharmacological drugs that inhibit 2D6 can produce an adverse reaction. Significant drug interactions that can inhibit cytochrome P450 2D6 include quinidine and cimetidine. Cimetidine increases bioavailability and decreases the clearance of this drug due to its inhibition of metabolic pathways of both demethylation and hydroxylation, as well as its ability to reduce hepatic extraction of nortriptyline. Other drugs are substrates for CYP2D6, such as other antidepressants, phenothiazines, and type-1C antiarrhythmics such as propafenone and flecainide. [25][26]

Concurrent usage of nortriptyline with drugs that can inhibit cytochrome CYP2D6 may require lower doses than usually prescribed for either nortriptyline or the other medication.

Many patients prescribed nortriptyline may already be taking SSRIs such as fluoxetine. If the benefit of switching from fluoxetine to nortriptyline is higher than the risk, the clinician should consider that fluoxetine has an active metabolite, norfluoxetine, with a long half-life. The risk of adverse effects and interactions may be high for several weeks after discontinuing fluoxetine. Therefore, usage of nortriptyline with SSRIs like fluoxetine can increase the risk for serotonin syndrome. Fluoxetine should be discontinued for up to six weeks before starting another medication that inhibits serotonin reuptake. If serotonin syndrome occurs, clinicians should promptly administer an antidote, i.e., cyproheptadine. Cyproheptadine is a 5-HT1A, 5-HT2A, and h2 receptor antagonist.[27]

Contraindications

Tricyclic antidepressants use along with a monoamine oxidase (MAO) inhibitor, linezolid, and IV methylene blue is contraindicated as they can lead to an increased risk of developing serotonin syndrome. Serotonin syndrome can be life-threatening as it can cause a change in mental status, autonomic instability, neuromuscular changes, seizures, and gastrointestinal symptoms. More importantly, concurrent use of both medications can cause convulsions, hyper-pyretic crises, and death. The patient must discontinue MAO inhibitors for at least 14 days before starting nortriptyline.[28] If nortriptyline must be used alongside serotonergic drugs such as triptans, other TCAs, fentanyl, lithium, tramadol, buspirone, tryptophan, and St. John’s Wort, the benefits must outweigh the risks.

Postmarketing reports have shown a possible association between nortriptyline and the unmasking of Brugada syndrome. For this reason, patients with confirmed or suspected Brugada syndrome should avoid nortriptyline as it can result in EKG abnormalities, syncope, and even sudden cardiac death.[29] Nortriptyline can cause pupillary dilation, potentially resulting in an angle-closure attack in an individual with anatomically narrow angles. Finally, nortriptyline is contraindicated during the acute recovery period after myocardial infarction. The use of nortriptyline is also contraindicated in patients with hypersensitivity to nortriptyline or its components. Cross-sensitivity between nortriptyline hydrochloride and other dibenzazepines is a possibility.

Monitoring

As an antidepressant, the therapeutic range for nortriptyline is between 50 to 150 ng/mL (190 to 570 nmol/L). According to APA guidelines, patients using nortriptyline need monitoring for suicidal ideation, especially at the start of therapy and when making dosage changes. Clinicians should frequently monitor cardiac parameters such as heart rate, EKG, and blood pressure in adults who already have existing cardiac disease and elderly patients.[28]

Monitor for improvement/worsening of depression using questionnaires such as PHQ-9 (Patient Health Questionnaire-9), which are patient-reported outcomes[30], and the Montgomery-Asberg Depression Rating Scale (MADRS), which is based on clinical judgment. [31] Integration of clinical decision support tools (CDS tools) in EHR can improve the administration of questionnaires and management of depression.[32]

Toxicity

Like many other TCAs, the toxicity of nortriptyline can be very harmful to the body. During an overdose, there is a blockade of the following receptors: sodium channels (fast) in the heart, muscarinic Ach receptors (central and peripheral), alpha-1 receptors in the periphery, and h2 and GABA-A in the central nervous system. Therefore, the most crucial initial step when assessing a patient with toxicity is ensuring the patient can adequately breathe. Intubation is usually mandatory for airway protection and proper ventilation. In addition, the clinician can administer IV fluids for hypotension.

Additionally, sodium bicarbonate is the recommended treatment for patients with prolonged QRS (greater than 100 milliseconds) or ventricular arrhythmia. The sodium bicarbonate dosage depends on the patient’s weight, usually 1 to 2 mEq/kg.  Arrhythmias not responding to sodium bicarbonate therapy may need lidocaine, phenytoin, or bretylium. TCAs can also cause seizures. These can have treatment with benzodiazepines such as lorazepam 2 mg or diazepam 5 mg, administered through the intravenous (IV) route. Treatment with activated charcoal for gastrointestinal decontamination is only indicated in patients who present within 2 hours of overdose (1 g/kg). Although there is a strong blockage of muscarinic acetylcholine receptors, physostigmine is contraindicated in the event of TCA toxicity as it can cause adverse cardiac effects such as cardiac arrest.[28] The principles of management of pediatric overdose are similar. However, It is recommended that the clinician contact the local poison control center for specific pediatric treatment.

Enhancing Healthcare Team Outcomes

Interprofessional healthcare team members, including clinicians, psychiatrists, nurse practitioners and physician assistants, nurses, and pharmacists, should be aware that nortriptyline is no longer a first-line choice for its indicated conditions. There are many better and safer antidepressants on the market. The drug has many side effects, which are often not well tolerated.[33] 

However, when a patient is taking nortriptyline, all interprofessional team members should contribute from their individual disciplines to ensure proper dosing, the absence of drug-drug interactions, and participate in patient monitoring and education, to drive optimal outcomes with minimal adverse events. Every team member is responsible for monitoring and counseling the patient and must be alert for signs of therapeutic failure, possible drug interactions, or adverse events, including toxicity. If they note an issue with the patient, they should report these to the other team members and document their observations in the patient’s medical record. A randomized controlled trial aimed at the clinical effectiveness of collaborative care in managing patients with moderate to severe depression showed optimistic results. Coordinated care between health care providers had continued promising results up to one year after initiation of the depression treatment and was preferred by patients. [34] [Level 2]

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Johnson KM, Devine JM, Ho KF, Howard KA, Saretsky TL, Jamieson CA. Evidence to Support Montgomery-Asberg Depression Rating Scale Administration Every 24 Hours to Assess Rapid Onset of Treatment Response. J Clin Psychiatry. 2016 Dec;77(12):1681-1686. [PubMed: 28086004]

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Maten N, Kroehl ME, Loeb DF, Bhat S, Ota T, Billups SJ, Schilling LM, Heckman S, Reingardt C, Trinkley KE. An evaluation of clinical decision support tools for Patient Health Questionnaire-9 administration. Ment Health Clin. 2021 Sep;11(5):267-273. [PMC free article: PMC8463004] [PubMed: 34621601]

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Riediger C, Schuster T, Barlinn K, Maier S, Weitz J, Siepmann T. Adverse Effects of Antidepressants for Chronic Pain: A Systematic Review and Meta-analysis. Front Neurol. 2017;8:307. [PMC free article: PMC5510574] [PubMed: 28769859]

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Richards DA, Hill JJ, Gask L, Lovell K, Chew-Graham C, Bower P, Cape J, Pilling S, Araya R, Kessler D, Bland JM, Green C, Gilbody S, Lewis G, Manning C, Hughes-Morley A, Barkham M. Clinical effectiveness of collaborative care for depression in UK primary care (CADET): cluster randomised controlled trial. BMJ. 2013 Aug 19;347:f4913. [PMC free article: PMC3746956] [PubMed: 23959152]

Disclosure: Gagindip Merwar declares no relevant financial relationships with ineligible companies.

Disclosure: Jonathan Gibbons declares no relevant financial relationships with ineligible companies.

Disclosure: Seyed Alireza Hosseini declares no relevant financial relationships with ineligible companies.

Disclosure: Abdolreza Saadabadi declares no relevant financial relationships with ineligible companies.

Nortriptyline: a medicine used to treat nerve pain and depression

1. About nortriptyline

Nortriptyline is a medicine used for treating nerve pain.

Occasionally, it’s also used to treat depression and bedwetting in children (nocturnal enuresis) .

Nortriptyline is available on prescription. It comes as tablets.

2. Key facts

• If you take nortriptyline to treat nerve pain, it usually takes a week or so for pain to begin to wear off.
• If you take it for depression, it can take 4 to 6 weeks until it reaches full effect.
• Common side effects include a dry mouth and constipation. They’re usually mild and go away after a couple of weeks.
• Nortriptyline can make you feel sleepy so it’s best to take it in the evening or before you go to bed.
• If your doctor decides to take you off nortriptyline, they will reduce your dose gradually to help prevent withdrawal side effects such as muscle pain or feeling sick or tired.

3. Who can and cannot take nortriptyline

Most adults can take nortriptyline. Teenagers aged 12 to 17 years can take it for depression.

Children aged 6 to 17 years old can also take it for bedwetting but other medicines are used first which have less side effects.

Nortriptyline is not suitable for some people. Check with your doctor before starting to take nortriptyline if you:

• have ever had an allergic reaction to nortriptyline or any other medicine
• have a heart problem – nortriptyline can make some heart problems worse
• have liver or kidney problems
• have epilepsy or are having electroconvulsive treatment (ECT) – nortriptyline can increase your risk of seizures or fits
• have ever taken any medicines for depression – some antidepressants can affect the way nortriptyline works, even after you’ve stopped taking them
• are pregnant, trying to get pregnant or breastfeeding
• have glaucoma – nortriptyline can increase the pressure in your eye
• have thoughts about harming yourself or ending your life
• have type 1 or type 2 diabetes – if you have diabetes, nortriptyline may affect your blood sugar levels. If you usually test your blood sugar level, you may have to do this more often for the first few weeks of treatment. Talk to your diabetes nurse or doctor if the reading is high or low

4. How and when to take nortriptyline

You’ll usually take nortriptyline once a day. If you take it once a day, it’s best to take it before you go to bed as it can make you feel sleepy. If you find that it’s affecting your sleep, you could try taking it earlier in the evening.

This medicine does not usually upset your stomach. You can take it with or without food.

Swallow the tablets whole, with a drink of water. If you chew them, they taste bitter.

Dosage and strength

Nortriptyline tablets come in 3 different strengths, 10mg, 25mg or 50mg.

The usual dose to treat nerve pain in adults is 10mg a day. This can be increased if necessary. The maximum dose of nortriptyline for treating pain is 75mg a day, but this is only under the supervision of a pain specialist.

For depression in adults, the dose is increased gradually to between 75mg and 100mg a day. It can be increased to a maximum dose of 150mg a day if a specialist prescribes it.

For depression in teenagers (12 to 17 years), the dose is usually increased gradually to 30mg to 50mg a day, but higher doses may be needed.

What if I forget to take it?

If you forget a dose, take it as soon as you remember, unless it’s nearly time for your next dose. In this case, just leave out the missed dose and take your next dose at the usual time.

Never take 2 doses at the same time to make up for a forgotten dose.

If you often forget doses, it may help to set an alarm to remind you. You could also ask your pharmacist for advice on other ways to help you remember to take your medicine.

What if I take too much?

Urgent advice: Contact 111 for advice now if:

• you take more than your usual dose of nortriptyline

Go to 111.nhs.uk or call 111

Taking too much nortriptyline can cause serious side effects such as a change in your heartbeat, or you may have a seizure or fit.

5. Side effects

Like all medicines, nortriptyline can cause side effects in some people, but many people have no side effects or only minor ones.

Some of the common side effects of nortriptyline will gradually improve as your body gets used to the medicine.

Common side effects

Doses of nortriptyline for pain are lower than the doses for depression. This means the common side effects tend to be milder and go away within a few days.

Keep taking the medicine but talk to your doctor or pharmacist if these side effects bother you or do not go away:

• constipation
• feeling dizzy
• dry mouth
• feeling sleepy
• difficulty peeing
• headaches

Serious side effects

It happens rarely, but some people have a serious side effect after taking nortriptyline.

Contact a doctor if:

• your heartbeat becomes fast and irregular
• the whites of your eyes turn yellow, or your skin turns yellow, although this may be less obvious on brown or black skin – these can be signs of a liver problem
• you have a headache that does not get better, feel confused or weak and have muscle cramps – together these can be signs of low sodium levels in your blood
• you have thoughts about harming yourself or ending your life
• you have eye pain, a change in your eyesight, or swelling or redness in or around the eye
• you have constipation that lasts a long time or problems peeing which are causing stomach ache

Immediate action required: Call 999 or go to A&E if:

• you have weakness on one side of your face or body, trouble speaking or thinking, loss of balance or blurred eyesight – these can be signs of a stroke
• you have a seizure or fit
• you get severe chest pain – this can be a sign of a heart attack

Serious allergic reaction

In rare cases, it’s possible to have a serious allergic reaction (anaphylaxis) to nortriptyline.

Immediate action required: Call 999 or go to A&E now if:

• you get a skin rash that may include itchy, red, swollen, blistered or peeling skin
• you’re wheezing
• you get tightness in the chest or throat
• you have trouble breathing or talking
• your mouth, face, lips, tongue or throat start swelling

You could be having a serious allergic reaction and may need immediate treatment in hospital.

These are not all the side effects of nortriptyline. For a full list see the leaflet inside your medicines packet.

Information:

You can report any suspected side effect using the Yellow Card safety scheme.

Visit Yellow Card for further information.

6. How to cope with side effects of nortriptyline

What to do about:

• constipation – get more fibre into your diet such as fresh fruit, vegetables and cereals. Try to drink several glasses of water or squash every day. If you can, it may also help to increase your level of exercise.
• feeling dizzy – this is probably due to low blood pressure. Drink plenty of water or squash. Do not stand up too quickly after you’ve been sitting or lying down. Do not drive, cycle or use tools or machinery until this feeling passes. It’s best not to drink alcohol until you see how the medicine affects you.
• dry mouth – chew sugar-free gum or have some sugar-free sweets.
• feeling sleepy – take nortriptyline in the evening. It’s best not to drink alcohol until you see how the medicine affects you. Do not drive, cycle or use tools or machinery while you’re feeling sleepy.
• difficulty peeing – try to relax when you pee. Do not try to force the flow of urine. If it does not happen, try again later. Talk to your doctor urgently if you cannot pee at all.
• headaches – make sure you rest and drink plenty of fluids. It’s best not to drink alcohol until you see how the medicine affects you. Try taking paracetamol or ibuprofen if you need pain relief. Talk to your doctor if the headaches last longer than a few days or are severe.

7. Pregnancy and breastfeeding

Nortriptyline and pregnancy

You may be advised to continue taking nortriptyline during pregnancy, especially if you take it to treat depression.

Speak to your doctor if you become pregnant while taking nortriptyline. Do not stop taking your medicine unless your doctor tells you to.

Your doctor can explain the risks and benefits of taking nortriptyline and will help you choose the best treatment for you and your baby.

Nortriptyline and breastfeeding

If your doctor or health visitor says your baby is healthy, you can use nortriptyline while breastfeeding.

Notriptyline passes into breast milk in very small amounts so it’s unlikely to cause any harm to your baby.

If you are being treated for depression it’s important to continue taking nortriptyline to keep you well. Breastfeeding will also benefit both you and your baby.

If you notice that your baby is not feeding as well as usual, or seems unusually sleepy, or if you have any other concerns about your baby, then talk to your health visitor or doctor as soon as possible.

Non-urgent advice: Tell your doctor if you’re:

• trying to get pregnant
• pregnant
• breastfeeding

For more information about how nortriptyline can affect you and your baby during pregnancy, read this leaflet on the Best Use of Medicines in Pregnancy (BUMPs) website.

8. Cautions with other medicines

Many medicines taken with nortriptyline can affect each other and increase the chance of side effects.

Always check with your doctor or a pharmacist before starting any new medicine while you are taking nortriptyline.

Taking opioid-based medicines, like codeine, morphine or oxycodone, together with nortriptyline can increase your risk of becoming very drowsy and having breathing problems.

Tell your doctor if you have ever taken any medicines for depression. Some antidepressants can affect the way nortriptyline works and cause very high blood pressure. This can happen even after you have stopped taking them.

Mixing nortriptyline with herbal remedies and supplements

Do not take St John’s wort, the herbal remedy for depression, while you are being treated with nortriptyline. It will increase your risk of side effects.

There’s very little information about taking nortriptyline with other herbal remedies and supplements. They are not tested in the same way as medicines.

Important:
Medicine safety

Tell your doctor or pharmacist if you’re taking any other medicines, including herbal medicines, vitamins or supplements.

9. Common questions about nortriptyline

How does nortriptyline work?

Nortriptyline is from a group of antidepressants called tricyclic antidepressants.

If you’re taking it for pain relief, it will change the way that your nerves receive pain signals so your pain goes away.

If you’re taking nortriptyline for depression, it’s thought to work by increasing a chemical called serotonin in the brain. This helps to improve your mood.

How long does it take to work?

If you take nortriptyline to treat nerve pain, it usually takes a week or so for pain to begin to wear off. You may start to sleep better at night.

If you take nortriptyline for depression, you may start to feel better after a couple of weeks. It can take 4 to 6 weeks until you feel the full benefits.

Do not stop taking nortriptyline after 1 to 2 weeks just because you feel it’s not helping your symptoms. Give it at least 6 weeks to work.

How will nortriptyline make me feel?

Although nortriptyline is an antidepressant, the doses are lower if you take it to help pain. Taking nortriptyline as a painkiller will not change your personality or make you feel any different.

If you’re taking nortriptyline for depression, it helps to lift your mood gradually so you feel better. You may get on with people more easily because you are less anxious.

Nortriptyline will not change your personality or give you a high of feeling happy. It will simply help you feel like yourself again.

Do not expect to feel better overnight though. Some people feel worse during the first few weeks of treatment before they begin to feel better.

What if I do not feel better?

When nortriptyline is taken for nerve pain, most people are able to sleep better within a few days and the pain starts to wear off after a week or so.

If your pain does not get better or you have side effects, talk to your doctor as there may be other treatments which work for you.

Talk to your doctor if you take nortriptyline for depression and you do not feel better after taking it for 6 weeks, or the side effects bother you.

How long will I take nortriptyline for?

If you take nortriptyline for pain, once your pain is under control, you’ll probably continue to take it for as long as it’s working for you. Some people take it for many months and even for years.

If you take nortriptyline for depression, it’s likely you’ll take it for several more months once you’re feeling better.

Most doctors recommend that you take antidepressants for 6 months to a year after you’ve stopped feeling depressed.

Stopping before then can make depression come back. Talk to your doctor about the risks and benefits of continuing to take nortriptyline for more than a few months.

Can I take nortriptyline long term?

For most people, nortriptyline is safe to take for a long time.

There do not seem to be any lasting harmful effects from taking nortriptyline for many months or years.

Is nortriptyline addictive?

Nortriptyline is not addictive but you can get withdrawal side effects if you stop taking it suddenly. You may have flu-like symptoms like feeling sick, muscle pain and feeling tired or restless.

To help prevent this happening, your doctor will probably recommend reducing your dose gradually over several weeks, or longer if you have been taking nortriptyline for a long time.

What will happen when I stop taking it?

You may get withdrawal side effects when you stop taking nortriptyline, especially if you stop taking it suddenly.

These side effects are a physical reaction as the medicine leaves your body. They can include sweating, being sick, feeling anxious, and difficulty falling asleep.

To help prevent them, your doctor will probably recommend reducing your dose gradually over several weeks, or longer if you have been taking nortriptyline for a long time.

Important

Do not stop taking nortriptyline suddenly, or without talking to your doctor.

Can I take nortriptyline with other painkillers?

Paracetamol and ibuprofen are safe to take with nortriptyline for a short time. Talk to your doctor if you need to take them for more than a few days.

Will it affect my sex life?

A few people have sex-related problems while they take nortriptyline. Both men and women may have changes in their sex drive.

Sexual side effects are not very common and should pass after the first couple of weeks. If they do not, and this is a problem for you, go back to your doctor to see if there’s another medicine you can try.

How is nortriptyline different to other medicines for nerve pain?

Nortriptyline is usually prescribed by your doctor if other painkillers, such as paracetamol and ibuprofen, have not worked.

Nortriptyline does not work any better or worse than other medicines for nerve pain.

How is it different to other antidepressants?

Nortriptyline does not work any better or worse than other antidepressants. However, sometimes people respond better to one antidepressant than another.

The best antidepressant for you depends on your symptoms and what medicines have worked for you in the past.

Talk to your doctor if you are not feeling any better after taking nortriptyline for 6 weeks or if the side effects still bother you.

Will I gain or lose weight?

Nortriptyline can change how hungry you feel. Some people feel more hungry when they’re taking it, and others feel less hungry. So your weight may change when you first start taking it.

If you start to have problems with your weight while taking nortriptyline, talk to your doctor or pharmacist.

Can I drink alcohol with it?

You can drink alcohol while taking nortriptyline but it may make you feel sleepy. It might be best to stop drinking alcohol until you see how the medicine makes you feel.

Are there foods and drinks I should avoid?

Apart from being extra careful with alcohol, you can eat and drink normally while taking nortriptyline.

Will it affect my contraception?

Nortriptyline does not affect any type of contraception including the combined pill and emergency contraception.

Will it affect my fertility?

There’s no clear evidence to suggest that nortriptyline affects fertility in either men or women.

However, speak to your doctor or a pharmacist before taking nortriptyline if you’re trying to get pregnant.

Can I drive or ride a bike?

Some people feel sleepy while they’re taking nortriptyline. It’s best to stop driving, cycling or operating machinery for the first few days and after each dose increase, until you know how this medicine makes you feel.

Will recreational drugs affect nortriptyline?

Cannabis with nortriptyline can make you feel very sleepy, especially if you’ve just started taking it. Cannabis can also give you a fast heartbeat.

It may be dangerous to take nortriptyline with:

• methadone
• stimulants like MDMA (ecstasy) or cocaine
• hallucinogens like LSD
• novel psychoactive substances (these used to be called “legal highs”) like mephedrone

Nortriptyline has not been properly tested with recreational drugs. Talk to your doctor if you think you might use recreational drugs while taking nortriptyline.

Why it is dangerous to use antidepressants on your own, and how to do it right / Sudo Null IT News

There are no drugs without side effects. More precisely, there is, but doctors do not classify extracts from the liver of the Barbary duck, diluted to the state of interstellar vacuum, as medicines. Antidepressants, for all their long history, are still serious drugs that require an individual approach and careful collaboration between the doctor and the patient.

The key question most often worries patients is “Will I become addicted to the drug?”.

After reading the forums for a long time, which in itself is not always a good idea, two more are often added:

1. Will I have problems in my sex life during and after taking the drug?
2. Will I gain weight?

That’s what we’ll talk about today. Antidepressants are more likely to have unwanted side effects on libido and may cause weight gain. Fortunately, if the clinical situation permits, these effects can be tried to be used correctly.

In particular, I will tell you why one of the atypical antidepressants was previously used instead of Viagra, whether it is possible to run in circles with benefit, and why fluvoxamine accidentally reduced the risks of hospitalization for covid.

Risks of addiction

Here, fortunately, everything is quite simple. There is none of them. Numerous studies show that antidepressants are not addictive drugs.

In the past century, two drugs were synthesized that carried certain risks of abuse, and these drugs are not currently in use:

1. Tranylcypromine
2. Amineptine

But there the situation was a little different. I told you earlier that we have a key triad of neurotransmitters that we act on – serotonin, norepinephrine and dopamine. Dopamine is the key biogenic amine that regulates our motivation system. If the intake of a substance causes an increase in its concentration, a person receives a positive reinforcement, a kind of praise from his own brain.

It is because of their specific effects on the dopamine pathways that these drugs have an amphetamine-like effect. A person experiences a surge of strength, he does not want to sleep. All this leads to the risks of abuse. Therefore, drugs are prohibited for use.

You can try comparing antidepressants and addictive drugs.

Narcotic: after a single dose, it causes a pleasant state. For example, cheerfulness and euphoria. And this is exactly what makes a person accept it a second and subsequent times.

Antidepressant: after taking the pill, is it supposed to be cool? I’ve never heard of such a thing. Without dosage titration, a person will be very lucky if side effects do not appear. The most frequent – nausea – somehow does not pull on a pleasant state.

Narcotic: as a result of the development of tolerance, narcotic substances are characterized by a continuous increase in dose. That is, the addict is forced to receive ever larger doses to achieve the effect, hence the phenomenon of overdose.

Antidepressant: the drug works in a therapeutic window – from one number of mg to another. Therefore, the increase in dosage does not occur immediately, individually and within this window. Does it make sense to use a pack of antidepressants every day to get pleasure? Not the slightest. The number of side effects will increase, but the effect will not, because it is extremely cumulative.

Drug: if you do not get a dose, then there is a “withdrawal”. And so strong that it is unrealistic to survive this breakdown at home. That is why drug treatment clinics are like prisons in Europe: clean, comfortable, but under supervision.

Antidepressant: Here one can say that when an antidepressant is withdrawn, a withdrawal syndrome occurs. And this is absolutely true if the withdrawal is abrupt at the therapeutic dosage. Getting out of the drug takes time, usually about 2-4 weeks – the body needs to get used to the fact that now it will have to work on its own, without a magic pendel. And there is a big difference between the unpleasant side effects that occur when you stop taking it and the painful craving for another dose. There is no sudden desire to go and throw a handful of pills with the abolition of antidepressants.

The bottom line is that antidepressants are not addictive and are completely useless for recreational use.

Difficulties with libido

The brain is an extremely complex system with a huge number of feedbacks. It is almost impossible to act on some aspect of a mental state in isolation and not get side effects. Serotonin in the main triad of neurotransmitters plays a key role in terms of both positive and undesirable side effects.
Serotonin exerts its regulatory effect by binding to numerous types of receptors from the 5-HT family. We are primarily interested in those responsible for key functions in the central nervous system – these are 5-HT ₁ and 5-HT ₂ .

It is these receptors that are targeted by SSRI drugs – selective serotonin reuptake inhibitors. More often, antidepressants of this type are key drugs in the treatment of anxiety disorders. In the normal version, the neuron tries to transmit excitation to its neighbor by throwing a neurotransmitter into the synaptic cleft. There, serotonin must bind to the receptors of another neuron and cause its excitation. Under the influence of SSRIs, the picture changes, the first neuron can no longer capture the excess neurotransmitter back, and the concentration of serotonin in the synaptic cleft gradually increases. It is much easier for the second neuron to get into an excited state, since its receptors now capture signal substances much more often. As a result of such therapy, the patient’s emotional background gradually normalizes and levels out, and habitual activity returns to him.

Everything is great. But the main problem is that the same 5-HT serotonin receptors are also responsible for regulating libido and orgasms. A meta-analysis shows that up to 70% of patients complain of sexual dysfunction during therapy. This effect is primarily due to an increase in serotonin levels and stimulation of the corresponding receptors. These receptors regulate several important things related to each other:

1. Libido is the very desire for sexual contact and the feeling of attraction.
2. Sensitivity of erogenous zones.
3. Orgasm intensity.

In fact, while the broken serotonin system is being restored, the brain is simply not up to sex. Most patients want less, and the sexual intercourse itself becomes longer due to a decrease in the sensitivity of the receptors.

Not everything is as scary as it seems, in fact. The effect of reducing libido is highly dependent on the drug chosen.

If small doses of an antidepressant are enough for the patient to treat the main problem, then often there are no special difficulties in sexual life. Although this is not a strict rule. Moreover, there is often a pronounced decrease in libido even with small dosages, so there is no point in “halving” the dosage.

It happens that patients say that they cannot get an orgasm during sexual intercourse, but pay attention to the fact “it is time to change the chandelier, as it does not fit the wallpaper”.

In men, on the other hand, there is good news: an increased level of serotonin increases the threshold of arousal, which is required to achieve orgasm. And this means that the time before ejaculation increases.

What can calm a person at an appointment? After completion of the course of treatment, the side effects completely disappear and libido is restored.

Interestingly, there are antidepressants with the opposite effect. Although this is not of great clinical importance, it would be interesting to mention their atypical properties.

One such drug once on the market is bupropion. In 2016, the manufacturer left the Russian market and revoked the license. This atypical antidepressant selectively inhibits the reuptake of norepinephrine and dopamine. In parallel, it works as an antagonist of nicotinic acetylcholine receptors. Due to the absence of a serotonin component, it does not cause sexual dysfunction. What’s more, research has shown that it can actually increase libido even in non-depressed people. In a gender-matched, double-blind study that lasted 12 weeks, 63% of patients taking the drug experienced an improvement in sex drive, compared with 3% in the placebo group. Nevertheless, one must understand that this is not a silver bullet, but a drug with a bunch of side effects. Therefore, trying to find it in some way is definitely not worth it.

Of the antidepressants approved in Russia with a positive effect on libido, trazodone is available. It was created back in the late 1960s in Italy at the Angelini Research laboratory. The drug has an atypical effect. It stimulates 5-HT ₁ and simultaneously blocks 5-HT ₂ A, 5-HT ₂ C receptors. Conventional SSRIs and other antidepressants stimulate all serotonin receptors simultaneously. At the same time, it is the stimulation of type 1 receptors that gives a pronounced antidepressant and anti-anxiety effect, and the stimulation of type 2 receptors brings mainly those very undesirable side effects.

Trazodone may be given alone or in combination with SSRIs to counteract libido effects. But it is worth remembering that the drug itself has a very weak effectiveness for the treatment of depression and anxiety, but very effectively solves the problem of insomnia. Because of this, it cannot be used to treat depression. Dosages at which the patient begins to sleep on the go come earlier than the antidepressant effect.

In rare cases, it can cause painful erections that last for several hours. This condition is called priapism. In women, too, only the erection will be clitoral. Usually, patients simply increase libido, which even led to attempts to use it in this niche before the invention of Viagra. Only now this erection will be combined with a constant desire to sleep.

Excess weight

Effect of antidepressants on key mechanisms of regulation of eating behavior

Many antidepressants have an undesirable side effect in the form of weight gain. A person has a rather complex system of regulation of eating behavior, tied to a variety of receptors both in the gastrointestinal tract and in the central nervous system. Exposure to antidepressants can significantly interfere with the regulation of these mechanisms.

The most pronounced weight gain from those drugs that interact with several types of receptors that regulate eating behavior. This effect is especially pronounced in amitriptyline, mirtazapine and paroxetine. If you look at the illustration above, you can see that amitriptyline and mirtazapine put together an almost perfect combo, which leads to a sharp increase in appetite and the desire to eat something sweet. Amitriptyline is a very cool drug, considered the gold standard drug. It is the first and, therefore, the most studied drug in this group. But it has significant side effects. It is used if you need to get good pain therapy for chronic pain. For example, with headaches and back pain. But at the same time, the patient will have to count calories very carefully and, perhaps, fight the nausea that often comes from this drug. In principle, at high dosages (which are needed to treat depression and anxiety), there are often situations where the side effect in the form of nausea is so pronounced that body weight may even decrease in the short term.

The “improved” formula of this drug, Nortriptyline, has long been used abroad. It also (logically) belongs to the group of tricyclic antidepressants and is similar in its chemical structure to amitriptyline. However, compared to the latter, Nortriptyline has a moderate stimulating as well as mood-enhancing effect. Gives the most minimal sedative effect. Successfully struggles with hypochondriacal conditions. The antidepressant effect of the drug occurs quickly, already in the first two weeks of admission.

In fact, the risks of gaining weight are not always a bad thing. There is a group of patients who, on the contrary, suffer from insufficient body weight and at the same time have indications for the appointment of antidepressants. In this case, the doctor can use the usually undesirable effect to the benefit of the patient.

Most often, of course, appetite stimulation is considered a negative side effect, especially in patients who have to take drugs for a long time. Therefore, in the case of overweight, the doctor tries to select drugs that either slightly affect appetite, or can even reduce it. A meta-analysis shows that some antidepressants can work effectively even in the complex therapy of obesity. One such drug is fluoxetine. This drug does not have a stable effect in the treatment of anxiety and depressive disorders, but either almost does not cause weight gain, or even reduces it and moderately improves mood.

That is why the choice of the drug should be discussed with the doctor. He can find the most suitable and safe option.

On the forums, I often come across a discussion of fluoxetine as a drug for rapid weight loss. In the recent past, when prescriptions were not so strictly asked in pharmacies, teenage girls who suffered from eating disorders literally bought it, because the drug did not give a feeling of hunger. Still, first of all, the problem of excess weight should be solved comprehensively and always with an endocrinologist. Fellow endocrinologists, for example, have been using a relatively new group of drugs for several years now – a synthetic analogue of GLP-1. Semaglutide from this group has a high safety and efficacy profile in the treatment of obesity, which is extremely interesting. The problem so far is that it is in Russia that such an application will be considered off-label, despite numerous studies and the expansion of its indications in other countries.

What else is interesting

If an antidepressant regulates not only the level of serotonin, but also other neurotransmitters, then the number of possible side effects increases significantly. This is especially common in patients who take SSRIs (serotonin + norepinephrine) and tricyclic antidepressants (serotonin, norepinephrine and dopamine). Stimulation of norepinephrine receptors strongly influences wakefulness levels, sleep, and fatigue build-up profile. I very often observe an interesting pattern in patients taking venlafaxine. If before the start of therapy during a depressive episode, they often complained of depression and unwillingness to get up in the morning, then after raising the level of norepinephrine, the picture changes dramatically. This neurotransmitter plays a key role in determining the activity of the reticular formation of the brain, which regulates the background level of wakefulness and excitability.

As a result, many patients begin to notice an altered wakefulness pattern. In the morning, awakening occurs almost instantly without any coffee, there is a feeling that you had enough sleep. Throughout the day, the patient is full of energy and often does not know what to do with excess energy. In the evening he does not feel like sleeping at all, and then suddenly it is as if the light is turned off, and the patient quickly falls asleep without an intermediate phase of sluggish activity and fatigue. In addition, the dream itself is changing. Many patients complain that they have intense vivid dreams. It’s even interesting once, but when you watch a dramatic story every night with a full taste-tactile presence, it can be exhausting.

If the side effect of norepinephrine becomes too severe, the patient may complain of being unable to sit still. He wants to dangle his legs, walk, run, jump or do at least some physical work, his feet and palms are wet from the stimulation of norepinephrine receptors, and the body asks for exercise. One of my patients during the adjustment period came to the point that he ran up the stairs in the office to the eighth floor and back every few hours. Sitting still was simply unbearable for him. In this case, dosage adjustments had to be made as mediator levels increased too rapidly. That is why constant feedback between the attending physician and the patient is very important. Normally, such pronounced effects can and should be avoided.

Balancing side effects

I would like to end this post with a very important thought. Neurologists and psychiatrists often face the side effects of their key drugs in the first weeks of use, patients’ fears, and common myths about these drugs. And the main task of the doctor is not only to be able to help the patient with his main complaints and disorders, but to be able to explain to the patient the need for admission, calm down and individually take into account all the additional effects of the drug. Now the neurologist has a very large selection of drugs in his arsenal, which allows him to effectively combine them and select the optimal combinations and regimens for each individual patient.

It is very good if the unwanted side effect can be made positive. To do this, you need to carefully interview the patient and spend a lot of time collecting an anamnesis:

• Does SSRI make it difficult to achieve orgasm? This can be a plus for premature ejaculation.
• Patient unable to gain weight? Consider mirtazapine.

In most applications, we cannot avoid all the negative effects of antidepressants, but constant monitoring and feedback from the attending physician will help to level them.

I always offer the patient two options:

1. The ability to quickly enter the drug. In this case, we will see a fairly quick effect that is needed in the treatment of a particular disease or disorder, but the side effects can be extremely difficult to survive and endure.
2. Or we slowly titrate the dosage and, accordingly, we do not immediately get the effect. Most often, this effect will be visible on the 4-6th week of admission. But due to small dosages, the body easily adapts and there will be no pronounced side effects.

In any case, each patient is individual. Everyone needs to be talked to and everyone needs to be heard. And choose a plan of action together. In an ideal situation, this will allow the patient to achieve a stable remission, normalize their lifestyle and do without pharmacological support in the future.

P.S. If you get to the clinic where I accept – “Our Time”, then say that you are from Habr: there will be a 5% discount on services.

Tension headache – treatment, symptoms, causes, diagnosis

Tension-type headache is usually diffuse, mild to moderate in intensity, and is often described as having a “tight band” sensation around the head. Tension-type headache (THT) is the most common type of headache, and yet the causes of this type of headache are still not well understood.

The treatment of tension headache is quite effective. Tension-type headache management is often a balance between a healthy lifestyle, the use of non-drug treatments, and the administration of adequate medication.

Symptoms

Symptoms of tension headache include:

• Dull, aching headache
• Feeling of “tightness” or pressure in the forehead or on the sides of the head and in the back of the head
• Soreness of the scalp, neck and shoulder muscles

Tension headaches fall into two main categories – episodic and chronic.

Episodic tension headaches

Episodic tension headaches can last from 30 minutes to a week. Episodic tension headaches occur on less than 15 days per month for at least three months. Frequent episodic tension headaches can become chronic.

Chronic tension headaches

This type of tension headache lasts several hours and may be continuous. If headaches occur 15 days or more per month for at least three months, they are considered chronic.

Tension headaches and migraine

Tension headaches are sometimes difficult to distinguish from migraines. In addition, if a patient has frequent episodic tension-type headaches, they may also have migraines.

Unlike some forms of migraine, tension headaches are usually not accompanied by blurred vision, nausea, or vomiting. And if, with migraine, physical activity increases the intensity of the headache, then with a headache, stress loads do not have such an effect. Hypersensitivity to any light or sound can sometimes occur with tension headaches, but these symptoms are uncommon.

Causes

Causes of tension headache are not known. Medical experts believed that tension headaches are due to problems in the muscles of the face, neck and scalp, which in turn are due to strong emotions, excessive workload or stress. But studies show that muscle spasm is not the cause of this type of headache.

The most common theories are that people who have tension headaches and may have stress sensitivity are hypersensitive to pain. Increased muscle soreness, which is a common symptom of tension-type headache, may be the result of an increase in overall pain sensitivity.

Triggers

Stress is the most common trigger that causes tension headaches.

Risk factors

Risk factors for tension headache include:

• Gender. Women are more likely to get this type of headache. One study found that almost 90 percent of women and 70 percent of men experience tension headaches during their lifetime.
• Mean patient age. The frequency of tension-type headaches peaks at age 40, although this headache can develop at any age.

Complications

Due to the fact that headaches can be quite frequent, this can significantly affect productivity and quality of life in general, especially if they become chronic. Frequent pain can disrupt the usual way of life and overall performance.

Diagnosis

Diagnosis of tension-type headache is primarily based on clinical history and symptoms and neurological findings.

Physicians may be interested in answers to the following questions:

• When did the symptoms start?
• Did the patient notice any triggers such as stress or hunger?
• Were the symptoms continuous or episodic?
• How severe are the symptoms?
• How often do headaches occur?
• How long did you have a headache for the last time?
• What does the patient think reduces symptoms and what makes symptoms worse?

In addition, the doctor is also interested in the following details:

• Characteristics of pain. Does the pain throb? Is the pain dull, constant, or sharp?
• Pain intensity. A good indicator of headache severity is the amount of time a patient can work during a headache attack. Can the patient work? Are there episodes in which the headache led to awakening from sleep or sleep disturbance?
• Localization of pain. Does the patient feel pain in the whole head, only on one side of the head, or just in the forehead or eye sockets?

Instrumental methods of examination

If the patient has unusual or severe headaches, the doctor may order an additional examination to rule out more serious causes of headaches.

The two most commonly used diagnostic methods, such as CT (computed tomography) and MRI, allow visualization of organs and tissues and detect morphological changes.

Treatment

Some patients with tension-type headache do not go to the doctor and try to treat the pain themselves. Unfortunately, repeated self-use of painkillers can itself cause severe headaches.

Medications

There is a wide variety of medicines, including over-the-counter medicines, to relieve pain, including:

• Painkillers. Simple over-the-counter pain relievers are usually the first line of treatment for headaches. These include aspirin, ibuprofen (Advil, Motrin IB, others), and naproxen (Aleve). Prescription drugs include naproxen (Naprosyn), indomethacin (Indocin), and ketorolac (ketorolac tromethamine).
• Combined preparations. Aspirin or acetaminophen, or both, often combined with caffeine or a sedative in the same medication. Combination preparations may be more effective than single-drug preparations.
• Triptans and drugs. For people who have both migraine and tension headaches, triptans can effectively relieve the headache. Opioids, or narcotics, are rarely used because of their side effects and the high risk of addiction.

Preventive drugs

Other drugs may be prescribed to reduce the frequency and severity of attacks, especially if the patient has frequent or chronic headaches that are not relieved by pain medication.

Prophylactic drugs may include:

• Tricyclic antidepressants. Tricyclic antidepressants, including amitriptyline and nortriptyline (Pamelor), are the most commonly used drugs for preventing tension-type headache. Side effects of these drugs may include weight gain, drowsiness, and dry mouth.
• Other antidepressants. There is evidence that antidepressants such as venlafaxine (Effexor XR) and mirtazapine (Remeron) are effective in patients who are also not depressed.
• Anticonvulsants and muscle relaxants. Other drugs that may prevent tension headaches from developing are anticonvulsants such as topiramate (Topamax) and muscle relaxants.

Lifestyle adjustments and home remedies

Rest, ice packs or long, hot showers can often relieve headaches.

Non-pharmacological treatment

• Acupuncture. Acupuncture can provide temporary relief from chronic tension headache.
• Massage.